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Terça-feira, 23.06.15

NW Bio Announces Data to Date From DCVax®-Direct Phase I Trial

01JUN2015

NW Bio Announces Data to Date From DCVax®-Direct Phase I Trial

 

86% of Phase I patients treated with preferred method still alive

 

Bethesda, MD, June 1, 2015– Northwest Biotherapeutics (NASDAQ: NWBO) (“NW Bio”), a U.S. biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, over the weekend in Chicago released promising new data on their Phase I trial of DCVax-Direct for direct injection into all types of inoperable solid tumors.

The patients enrolled in the trial had late stage cancers, with an average of three inoperable tumors.  The patients had failed multiple prior therapies and had a poor prognosis.

The trial enrolled 40 patients, and 39 were evaluable.  A conservative treatment regimen was used.  Although the patients had multiple inoperable tumors, only 1 tumor was injected with DCVax-Direct.  The treatments included only 3 injections in the first 2 weeks (Day 0, 7 and 14), and up to 3 additional injections spaced months apart thereafter (Weeks 8, 16 and 32), over a total period of 8 months.

Patients typically received their first injection about 1-1/2 months after recruitment.  Four patients are still in the process of completing the study visits, and data collection is ongoing on all of the patients.

The trial tested three different dose levels of DCVax-Direct, two different methods of activating the dendritic cells that comprise DCVax-Direct, and a dozen different cancers.  Findings to date include encouraging survival data and substantial induction of immune checkpoint expression (PD-L1).

The webcast and presentation by Dr. Bosch can be found on the Company’s website at nwbio.com/webcast

Findings to date include the following:

  • 27 of 39 patients are still alive at up to 18 months after first injection.
  • Patient survival correlates with the method of dendritic cell activation used.  With the preferred method, 18 of 21 patients are still alive.
  • Treatment effects have been observed in diverse cancers, including lung, breast, colorectal, pancreatic, sarcoma, melanoma, neuro-endocrine and other cancers.
  • Patient survival correlates with the number of DCVax-Direct injections.
  • Patient survival also correlates with stabilization of disease at Week 8 (4th injection visit).  Among patients treated with the preferred method of dendritic cell activation, 16 of 19 achieved stable disease (i.e., less than 25% increase in tumor size from baseline) at Week 8.

 

Findings to date relating to immunological responses include the following:

  • Induction of PDL-1 immune checkpoint expression was seen in 64% of evaluable patients (14 of 22) following DCVax-Direct treatment.  This suggests that the tumors are putting up defenses against the immune responses induced by DCVax-Direct, and marks these patients as potential candidates for treatment with checkpoint inhibitor therapies.
  • An increase in T-cell infiltration into tumors, by functionally active T-cells, was seen following DCVax-Direct treatment.
  • Both local effects (in the injected tumor) and systemic effects were observed.

 

Based on the findings from the Phase I trial, the Company plans to enhance its Phase II trials in several ways, including by:

  • Using only the preferred activation method of the DCVax dendritic cells.
  • Injecting multiple inoperable tumors at each treatment visit, not just one.
  • Providing more frequent treatments and a larger total number of treatments.

 

The Company plans to pursue Phase II trials in non-small cell lung cancer and sarcoma, as well as a Phase II trial for multiple diverse types of cancers similar to the Phase I study.   The Company also plans to expand the trial sites to include countries beyond the U.S.

“We are quite encouraged to see these results across diverse types of cancers, in late stage patients with multiple inoperable tumors who have exhausted other treatment options, and with quite a conservative DCVax-Direct treatment regimen” commented Linda Powers, CEO of NW Bio.  “We are looking forward to proceeding with Phase II trials applying the lessons learned from this informative Phase I trial.”

 

About Northwest Biotherapeutics

Northwest Biotherapeutics is a biotechnology company focused on developing immunotherapy products to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both the U.S. and Europe.  The Company has a broad platform technology for DCVax® dendritic cell-based vaccines.  The Company’s lead program is a 348-patient Phase III trial in newly diagnosed Glioblastoma multiforme (GBM).  GBM is the most aggressive and lethal form of brain cancer, and is an “orphan disease.”  The Company is under way with a 60-patient Phase I/II trial with DCVax-Direct for all inoperable solid tumor cancers.  It has completed enrollment in the Phase I portion of the trial.  The Company previously received clearance from the FDA for a 612-patient Phase III trial in prostate cancer.  The Company conducted a Phase I/II trial with DCVax for metastatic ovarian cancer together with the University of Pennsylvania.  In Germany, the Company has also received approval of a 5-year Hospital Exemption for the treatment of all glioma (brain cancer) patients outside the clinical trial.

 

Disclaimer

Statements made in this news release that are not historical facts, including statements concerning future treatment of patients using DCVax and future clinical trials, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.  Words such as “expect,” “believe,” “intend,” “design,” “plan,” “continue,” “may,” “will,” “anticipate,” and similar expressions are intended to identify forward-looking statements.  Actual results may differ materially from those projected in any forward-looking statement.  Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as risks related to the Company’s ongoing ability to raise additional capital, risks related to the Company’s ability to enroll patients in its clinical trials and complete the trials on a timely basis, uncertainties about the clinical trials process, uncertainties about the timely performance of third parties, risks related to whether the Company’s products will demonstrate safety and efficacy, risks related to the Company’s and Cognate’s abilities to carry out the intended manufacturing expansions contemplated in the Cognate Agreements, risks related to the Company’s ability to carry out the Hospital Exemption program and risks related to possible reimbursement and pricing.  Additional information on these and other factors, including Risk Factors, which could affect the Company’s results, is included in its Securities and Exchange Commission (“SEC”) filings.  Finally, there may be other factors not mentioned above or included in the Company’s SEC filings that may cause actual results to differ materially from those projected in any forward-looking statement.  You should not place undue reliance on any forward-looking statements.  The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by securities laws.

 

CONTACTS

Les Goldman                          Michael Meehan (Media)        Farrell Kramer (Media)

202-841-7909                          202-262-9081                          212-710-9685

lgoldman@nwbio.com            mm@SQcomms.com              farrell.kramer@mbsvalue.com

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por cyto às 17:36

Terça-feira, 23.06.15

Scientists find new way of classifying brain cancers

Scientists find new way of classifying brain cancers

Published on June 11, 2015 at 6:17 AM 

Not all brain cancers are the same but together they represent a deadly disease that has been difficult to identify and treat. Scientists at multiple institutions have found a new way of classifying brain cancers that could very well change how the illness is diagnosed and treated.

The study, a project of The Cancer Genome Atlas, found striking molecular differences between various forms of gliomas or brain tumors.

"We found molecular signatures that better define clinical behavior based on our analysis," said W.K. Alfred Yung, M.D., chair of Neuro-Oncology at The University of Texas MD Anderson Center. "We hope this will impact how physicians both diagnose and plan therapies for brain cancer."

Yung and Roeland Verhaak, Ph.D., associate professor of Bioinformatics and Computational Biology at MD Anderson, were co-authors and study leads in an investigation that involved more than 300 scientists from multiple institutions.

"We looked at the six most common forms of glioma and were able to deduce that these can be effectively grouped into three distinct molecular super clusters of lower-grade gliomas," said Verhaak. "It is exciting that our findings are likely to provide a basis for the upcoming update to the WHO classification of tumors of the central nervous system."

The study looked at the molecular makeup of brain tumors including gene mutations, chromosomal abnormalities and other alterations. Results from the study were published in the June 10, 2015 issue of the New England Journal of Medicine.

The study represents a major step in classifying and treating brain tumors more precisely based on their genetic makeup, said Daniel J. Brat, M.D., Ph.D., a researcher and neuropathologist at Winship Cancer Institute of Emory University, Atlanta, and co-leader of the study.

The scientists believe that the use of the biomarkers in the diagnosis of these forms of brain tumors will lead to a much more consistent manner of diagnosis and patient management. The study, which involved 44 institutions, concluded that molecular tests in addition to standard histopathological examination under the microscope will be more accurate in indicating whether the disease is more aggressive or will respond to certain chemotherapies.

Source:

The University of Texas MD Anderson Center

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por cyto às 17:24

Terça-feira, 23.06.15

Johns Hopkins researchers develop new imaging technology to help remove brain tumors safely

Johns Hopkins researchers develop new imaging technology to help remove brain tumors safely

Published on June 18, 2015 at 7:38 AM 

Brain surgery is famously difficult for good reason: When removing a tumor, for example, neurosurgeons walk a tightrope as they try to take out as much of the cancer as possible while keeping crucial brain tissue intact — and visually distinguishing the two is often impossible. Now Johns Hopkins researchers report they have developed an imaging technology that could provide surgeons with a color-coded map of a patient's brain showing which areas are and are not cancer.

A summary of the research appears June 17 in Science Translational Medicine.

"As a neurosurgeon, I'm in agony when I'm taking out a tumor. If I take out too little, the cancer could come back; too much, and the patient can be permanently disabled," says Alfredo Quinones-Hinojosa, M.D., a professor of neurosurgery, neuroscience and oncology at the Johns Hopkins University School of Medicine and the clinical leader of the research team. "We think optical coherence tomography has strong potential for helping surgeons know exactly where to cut."

First developed in the early 1990s for imaging the retina, optical coherence tomography (OCT) operates on the same echolocation principle used by bats and ultrasound scanners, but it uses light rather than sound waves, yielding a higher-resolution image than does ultrasound. One unique feature of OCT is that, unlike X-ray, CT scans or PET scans, it delivers no ionizing radiation to patients.

For the past decade, research groups around the globe, including a group at Johns Hopkins led by Xingde Li, Ph.D., a professor of biomedical engineering, has been working to further develop and apply the technology to other organs beyond the relatively transparent eye. Carmen Kut, an M.D./Ph.D. student working in Li's lab, thought OCT might provide a solution to the problem of separating brain cancers from other tissue during surgery.

Working with Li, Quinones-Hinojosa and other collaborators, Kut first built on the idea that cancers tend to be relatively dense, which affects how they scatter and reflect lightwaves. The team tried for three years to build their technique on this principle. Eventually, the researchers figured out that a second special property of brain cancer cells — that they lack the so-called myelin sheaths that coat healthy brain cells — had a greater effect on the OCT readings than did density.

Once they had found the characteristic OCT "signature" of brain cancer, the team devised a computer algorithm to process OCT data and, nearly instantaneously, generate a color-coded map with cancer in red and healthy tissue in green. "We envision that the OCT would be aimed at the area being operated on, and the surgeon could look at a screen to get a continuously updated picture of where the cancer is — and isn't," Li says.

So far, says Kut, the team has tested the system on fresh human brain tissue removed during surgeries and in surgeries to remove brain tumors from mice. The researchers hope to begin clinical trials in patients this summer.

If those trials are successful and the system goes to market, it will be a big step up from imaging technologies now available during surgeries, says Quinones-Hinojosa. "Ultrasound has a much lower resolution than OCT, and MRI scanners designed to be wheeled over a patient on the operating table cost several millions of dollars each — and require an extra hour of operating room time to obtain a single image," he says. By comparison, the team anticipates that the cost of an OCT-based system would run in the hundreds of thousands of dollars.

The system can potentially be adapted to detect cancers in other parts of the body, Kut says. She is working on combining OCT with a different imaging technique that would detect blood vessels to help surgeons avoid cutting them.

 

Source:

Johns Hopkins Medicine

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por cyto às 17:23

Terça-feira, 23.06.15

NW Bio releases promising new data on DCVax-Direct Phase I trial for inoperable solid tumors

NW Bio releases promising new data on DCVax-Direct Phase I trial for inoperable solid tumors

Published on June 2, 2015 at 10:00 AM · 

Northwest Biotherapeutics (NASDAQ: NWBO) ("NW Bio"), a U.S. biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, over the weekend in Chicago released promising new data on their Phase I trial of DCVax-Direct for direct injection into all types of inoperable solid tumors.

The patients enrolled in the trial had late stage cancers, with an average of three inoperable tumors. The patients had failed multiple prior therapies and had a poor prognosis.

The trial enrolled 40 patients, and 39 were evaluable. A conservative treatment regimen was used. Although the patients had multiple inoperable tumors, only 1 tumor was injected with DCVax-Direct. The treatments included only 3 injections in the first 2 weeks (Day 0, 7 and 14), and up to 3 additional injections spaced months apart thereafter (Weeks 8, 16 and 32), over a total period of 8 months.

Patients typically received their first injection about 1-1/2 months after recruitment. Four patients are still in the process of completing the study visits, and data collection is ongoing on all of the patients.

The trial tested three different dose levels of DCVax-Direct, two different methods of activating the dendritic cells that comprise DCVax-Direct, and a dozen different cancers. Findings to date include encouraging survival data and substantial induction of immune checkpoint expression (PDL-1).

The webcast and presentation by Dr. Bosch can be found on the Company's website at nwbio.com/webcast

Findings to date include the following:

  • 27 of 39 patients are still alive at up to 18 months after first injection.
  • Patient survival correlates with the method of dendritic cell activation used. With the preferred method, 18 of 21 patients are still alive.
  • Treatment effects have been observed in diverse cancers, including lung, breast, colorectal, pancreatic, sarcoma, melanoma, neuro-endocrine and other cancers.
  • Patient survival correlates with the number of DCVax-Direct injections.
  • Patient survival also correlates with stabilization of disease at Week 8 (4th injection visit). Among patients treated with the preferred method of dendritic cell activation, 16 of 19 achieved stable disease (i.e., less than 25% increase in tumor size from baseline) at Week 8.

Findings to date relating to immunological responses include the following:

  • Induction of PDL-1 immune checkpoint expression was seen in 64% of evaluable patients (14 of 22) following DCVax-Direct treatment. This suggests that the tumors are putting up defenses against the immune responses induced by DCVax-Direct, and marks these patients as potential candidates for treatment with checkpoint inhibitor therapies.
  • An increase in T-cell infiltration into tumors, by functionally active T-cells, was seen following DCVax-Direct treatment.
  • Both local effects (in the injected tumor) and systemic effects were observed.

Based on the findings from the Phase I trial, the Company plans to enhance its Phase II trials in several ways, including by:

  • Using only the preferred activation method of the DCVax dendritic cells.
  • Injecting multiple inoperable tumors at each treatment visit, not just one.
  • Providing more frequent treatments and a larger total number of treatments.

The Company plans to pursue Phase II trials in non-small cell lung cancer and sarcoma, as well as a Phase II trial for multiple diverse types of cancers similar to the Phase I study. The Company also plans to expand the trial sites to include countries beyond the U.S.

"We are quite encouraged to see these results across diverse types of cancers, in late stage patients with multiple inoperable tumors who have exhausted other treatment options, and with quite a conservative DCVax-Direct treatment regimen," commented Linda Powers, CEO of NW Bio. "We are looking forward to proceeding with Phase II trials applying the lessons learned from this informative Phase I trial."

Source:

Northwest Biotherapeutics, Inc.

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por cyto às 17:20

Terça-feira, 23.06.15

Celldex's glioblastoma vaccine scores a clear survival benefit

ASCO: Celldex's glioblastoma vaccine scores a clear survival benefit

CHICAGO--Celldex has added another round of positive data demonstrating that its brain cancer vaccine rindopepimut--more formally called Rintega and less formally "rindo"--provided a clear though relatively modest average survival benefit for recurrent glioblastoma patients in a Phase II study. And with the initial data set from Phase III looming later in the year, the biotech is carefully moving forward with its ongoing dialogue with regulators to gauge just how receptive they may be to speeding up an approval.

MRI image of a glioblastoma tumor--Courtesy of NIH

In the drug arm, which received a combination of rindo plus Avastin, 45% of the patients in the Phase II were alive after 12 months of treatment, compared with 31% of the patients in the Avastin-only arm. The rindo group registered a median overall survival rate of 11.6 months compared with 9.3 months in the control. 

"This is the first data we know of that showed a statistically significant benefit in the survival setting," says Celldex ($CLDX) CEO Anthony Marucci, a feat that Avastin notably failed to accomplish. In addition, 17% of patients were able to stay off of steroids for more than a year, which Celldex scores as another notable potential benefit for patients.

 

 


These new data help sustain an ongoing discussion with the FDA about the possibility of accelerating an approval of this drug, which is remarkable for a variety of reasons. Glioblastoma remains one of the toughest targets in the cancer field and cancer vaccines in particular have a troubled history of failure.

But Marucci fingers their targeted approach to targeting EGFRvIII--or v3 in shorthand lingo--for their against-the-odds success, noting that they don't need a massive T cell response to wipe out the v3 cells to get a clear response.

Marucci and his crew at Celldex took some interim positive numbers from the Phase II to the FDA last fall to gauge its appetite for an accelerated approval pitch. The FDA didn't go for it at that time. But out of those discussions, says the CEO, the FDA handed out its coveted breakthrough therapy designation, which is intended to keep its doors open to advances just like this as they continue to review Celldex's case for a speedy approval.

Marucci treads carefully when he talks about pursuing an accelerated approval based on data from a study with 78 patients. Physicians and patients are eager to try new drugs for a ruthless and typically quick killer, so even though the median survival benefit wasn't stunning, the agency won't need to see spectacular responses before they act. Also, some more durable responses seen in this study could contribute an added element of hope for many people who currently don't have much to be positive about. But the agency may also want to wait to see at least initial data from the larger Phase III before it acts.

Celldex has had its ups and down with this cancer vaccine over the years. Pfizer dumped its collaboration with the biotech close to 5 years ago. Peak sales estimates, meanwhile, tend to gyrate between a few hundred million to more than $1 billion in annual revenue.

- here's the release

Related Articles:
Celldex jumps after gaining an FDA 'breakthrough'
Celldex glioblastoma vaccine extends survival in Phase II
Celldex shares rally (briefly) on positive PhII brain cancer data

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por cyto às 17:08

Terça-feira, 23.06.15

Tumor profiling on 1245 gliomas and paired tumor study on 19 high grade gliomas.

Tumor profiling on 1245 gliomas and paired tumor study on 19 high grade gliomas.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Poster Session, Central Nervous System Tumors
Abstract Number: 

2058

Poster Board Number: 
Board #47
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2058)
Author(s): 
Joanne Xiu, David Spetzler, Ryan Bender, Anatole Ghazalpour, Zoran Gatalica, Sandeep K. Reddy, David Eric Piccioni, Jethro Lisien Hu, Michael J. Glantz, Santosh Kesari; Caris Life Sciences, Phoenix, AZ; Caris Life Sci, Paradise Valley, AZ; UC San Diego Moores Cancer Center, San Diego, CA; Cedars-Sinai, Los Angeles, CA; Penn State - Milton S Hershey Medcl Ctr, Hinsdale, MA; UC San Diego, La Jolla, CA

Abstract Disclosures

Abstract: 

Background: Gliomas are molecularly heterogeneous with genetic alterations driving the growth of recurrences different from the initial tumor. Previous reports showed molecular changes during progression of lower grade gliomas to GBM, driving tumor growth and treatment resistance; however changes during progression of high-grade gliomas have not been systematically reported. Methods: 1245 glioma tumors (934 GBM) were tested with multiple platforms including sequencing (SEQ), immunohistochemistry (IHC), fluorescent/chromogenic in-situ hybridization (FISH/CISH), fragment analysis (FA) and promoter methylation (Me) assay. Metachronous paired tumors from 19 patients (pts) were assessed for biomarker changes over time. Results: EGFRvIII was seen exclusively in GBM (16% of GBM) while amplification was more common in GBM than grade II-III tumors (56% vs. 20%, p < 0.001). MGMT Me was seen in 47% of all, and was more common in grade II-III (64% vs. 42%, p < 0.001). PD-L1 expression on tumor cells was seen in 27% and was more common in tumors without MGMT Me (36% vs. 18%, p = 0.01). PD-1 expression on tumor-infiltrating lymphocytes was seen in 48% and was higher in GBM than grade II-III(54% vs. 30%, p = 0.005). 38 of 48 sequenced genes had mutations, including BRCA1 (8%) and BRCA2 (6%). 1p19q co-deletion was seen in 26% of grade II-III and 2.9% of GBM. Paired tumors from 19 pts (18 GBM and 1 grade III in both samples) taken at an average of 469 days apart (91-1400) showed that 17 pairs (89%) had one or more biomarker changes over time. 3 of 13 (23%) pairs lost MGMT Me, potentially indicating acquired resistance to temozolomide. EGFR aberrations including amplification (N = 1), mutations on the extracellular (EGFRvIII, N = 1) and intracellular domains (T790M, N = 1; Exon 20 insertion N = 1) were acquired in 3 pairs. One pt, presenting with a PTEN mutation, acquired three additional mutations: cKIT (E583K), PTPN11 (A72T) and PIK3CA (D434N). Conclusions: Multiplatform tumor profiling on a large cohort of gliomas confirms tumor heterogeneity. Changes in MGMT Me and EGFR of potential therapeutic importance are frequently observed in high grade gliomas at the time of recurrence, suggesting the need for a re-biopsy for tumor profiling to direct the next line of therapy.

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por cyto às 17:04

Terça-feira, 23.06.15

Phase I study of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly diagnosed glioblastoma multiforme (GBM).

Phase I study of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly diagnosed glioblastoma multiforme (GBM).

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
This abstract will not be presented at the 2015 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 

e13030

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr e13030)
Author(s): 
Gordana Vlahovic, Gerald E. Archer, Denise Lally-Goss, Elizabeth Reap, Annick Desjardins, Katherine B. Peters, Dina Randazzo, Patrick Healy, James Emmett Herndon, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, John H. Sampson; Duke University Medical Center, Durham, NC

Abstract Disclosures

Abstract: 

Background: The inherent biologic specificity of immunotherapy offers the prospect of targeting neoplastic cells more precisely. Dendritic cells (DCs) are endowed with an extraordinary ability to activate CD4+ and CD8+ T-cells, and DCs loaded with antigens derived from tumor cells (CMV pp65-LAMP mRNA) have the potential to induce potent antitumor immunity. Furthermore, regulatory T-cells (TRegs) which induce a state of reversible immunosuppression in MG and can be functionally inactivated with anti-CD25 antibody (Ab), while dramatically enhance vaccine-induced immune responses. Our pilot group of 7 pts that received DC CMV vaccine with one dose of anti-CD25 Ab had median progression free survival (PFS) and overall survival (OS) of 23.5 months and 30.3 months respectively. There were no adverse events associated with the vaccine or anti-CD25 Ab therapy. Methods:Eligible are gross totally resected pts with newly diagnosed GBM. Pts undergo leukapheresis followed by standard of care radiation/temozolomide (XRT/TMZ) therapy. After completion of XRT/TMZ, up to 12 cycles of TMZ is administered. On Day 21 of the 1st cycle of post-XRT TMZ Vaccine # 1 is administered. Vaccines #2-3 are given biweekly following vaccine #1. Anti-CD25 Ab (basiliximab) is given twice, one week before vaccines 1 and 2. In this dose escalation study two dose levels are examined: 20 or 40 mg. An additional vaccine is given with each cycle of TMZ to a total of 8. Pts were followed with serial MRIs until disease progression. Multiple time-point immuno-monitoring by kinetics of number of TRegs and pp65 specific T cells by INFγ ELISPOT is performed for each pt. Results: 21 pts are enrolled to Phase I and to date 8 pts (7 males) have received both administrations of basiliximab and are evaluable for the determination of maximum tolerated dose. 4 pts were screen failures. No DLT or adverse events attributable to treatment are observed thus far. Conclusions: Treatment with XRT/TMZ, DC vaccine and basiliximab was well tolerated. Clinical trial information: NCT00626483

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por cyto às 17:00

Terça-feira, 23.06.15

Phase II multicenter study of gene mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.

Phase II multicenter study of gene mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Clinical Science Symposium, Immunotherapy for Central Nervous System Tumors: Biomarkers and Novel Data
Abstract Number: 

2010

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2010)
Author(s): 
Laura K. Aguilar, Lee A. Wheeler, Andrea G. Manzanera, Susan D. Bell, Robert Cavaliere, John M. McGregor, Simon Lo, John C. Grecula, Herbert B. Newton, Behnam Badie, Todd W. Trask, David S. Baskin, Jana Portnow, Pamela Z. New, Estuardo Aguilar-Cordova, E. Antonio Chiocca; Advantagene Inc, Auburndale, MA; Brigham and Women’s Hospital/Harvard Medical School, Boston, MA; Ohio State University, Columbus, OH; Ohio State University Wexner Medical Center, Columbus, OH; City of Hope, Duarte, CA; Houston Methodist, Houston, TX; Brigham and Women's Hospital/Harvard Medical School, Boston, MA

Abstract Disclosures

Abstract: 

Background: New therapies are desperately needed for malignant gliomas since aggressive standard of care (SOC) treatment with surgery, radiation, and temozolomide leads to median survival of less than 15 months. Gene Mediated Cytotoxic Immunotherapy (GMCI) generates a polyvalent anti-tumor immune response through local delivery of aglatimagene besadenovec (AdV-tk) plus prodrug, synergizing with SOC to improve patient outcomes.Methods: A Phase II open-label multicenter trial was designed to assess safety and overall survival (OS) after GMCI+SOC compared to a concurrent matched control group meeting protocol criteria and SOC at an institution not active in the treatment trial. AdV-tk was injected into the resection bed followed by oral valacyclovir for 14 days. Primary efficacy analysis was planned on the null hypothesis of no improvement in the 2-year survival over the SOC group with planned subset analysis of significant disease prognostic factors. Results: From 2006 to 2010, 48 patients completed SOC+GMCI and 134 SOC in the matched cohort. There were no dose-limiting toxicities. Fever, fatigue, and headache were the most common GMCI-related symptoms. Median OS increased by 3.6 months, from 13.5 for SOC to 17.1 months for GMCI+SOC (p = 0.0417). Survival at 1- 2- and 3-years increased from 57%, 22%, and 8% to 67%, 35%, and 19%, respectively. The improvement was mostly in patients that underwent gross total resection: median OS increased from 16.9 to 25 months (p = 0.0492); 1- 2- and 3-year survival rates from 64%, 28% and 6% to 90%, 53% and 32%. Conclusions: GMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival rates compared favorably to historical reports and a matched control group. Survival outcomes were significantly improved in patients with minimal residual disease after total resection. The 2-year survival rate met the planned statistical threshold for significance. No significant differences were observed for subtotal resections. This is the first study to demonstrate a correlation between maximum debulking and a survival advantage using immunotherapy. These data strongly support further evaluation of GMCI for malignant gliomas. Clinical trial information: NCT00589875

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por cyto às 16:58

Terça-feira, 23.06.15

Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy.

Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Clinical Science Symposium, Immunotherapy for Central Nervous System Tumors: Biomarkers and Novel Data
Abstract Number: 

2011

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2011)
Author(s): 
Orin Bloch, Jeffrey J. Raizer, Michael Lim, Michael Sughrue, Ricardo Komotar, Jonathan Abrahams, Donald O'Rourke, Anthony D'Ambrosio, Jeffrey N. Bruce, Andrew Parsa; Northwestern University, Chicago, IL; Lurie Comp Cancer Ctr of Northwestern Univ, Chicago, IL; The Johns Hopkins Hospital, Baltimore, MD; University of Oklahoma, Oaklahoma City, OK; University of Miami, Miami, FL; Northern Westchester Hospital, Mount Kisco, NY; University of Pennsylvania, Philadelphia, PA; The Valley Hospital, Paramus, NJ; Columbia Univ, New York, NY

Abstract Disclosures

Abstract: 

Background: Standard therapy for glioblastoma (GBM) consists of surgical resection followed by concurrent chemo and radiotherapy with a median overall survival of 16 months. In this phase II, single arm study, addition of an autologous heat shock protein peptide vaccine was evaluated for newly diagnosed GBM. Expression of PD-L1 on peripheral monocytes has been shown to be elevated in GBM patients and was evaluated as a predictor of survival.Methods: Adult patients with GBM underwent surgical resection followed by chemoradiotherapy. Vaccine was generated from tissue obtained at surgery. Key eligibility criteria included ≥ 90% tumor resection and collection of sufficient tumor tissue to generate at least four 25 μg doses of vaccine. Within 5 weeks of completing radiotherapy, patients received weekly vaccinations, followed by adjuvant temozolomide with monthly vaccinations until depletion of vaccine or tumor progression. The primary endpoint was overall survival. Relative PD-L1 expression on circulating monocytes was measured from peripheral blood obtained at surgery. Results: A total of 46 patients from eight centers received the vaccine in addition to standard therapy. Median progression-free survival was 17.8 months (95% Confidence Interval [CI], 11.3-21.6) and median overall survival was 23.8 months (95% CI, 19.8-30.2). The vaccine was well-tolerated with no severe (grade 3 or 4) events attributed to vaccination. The median overall survival for patients with high PD-L1 expression (above the median, 54.5% of monocytes) was 18.0 months (95% CI, 10.0 – 23.3) as compared to 44.7 months (95% CI not calcuable) for low PD-L1 expressors (hazard ratio for death 3.35; 95% CI, 1.36 – 8.23; p = 0.003). A multivariate proportional hazards model revealed MGMT methylation status and PD-L1 expression as the greatest independent predictors of survival. Conclusions: Vaccination with autologous tumor-derived heat shock proteins improves survival compared to standard therapy for newly diagnosed GBM. Systemic immunosuppression driven by peripheral monocyte expression of PD-L1 is a previously unidentified factor that may mitigate vaccine efficacy. Clinical trial information: NCT00905060

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por cyto às 16:57

Terça-feira, 23.06.15

Does extent of resection matter in recurrent glioblastoma? Lessons from the DIRECTOR trial.

Does extent of resection matter in recurrent glioblastoma? Lessons from the DIRECTOR trial.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Poster Session, Central Nervous System Tumors
Abstract Number: 

2041

Poster Board Number: 
Board #30
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2041)
Author(s): 
Bogdana Suchorska, Michael Weller, Ghazaleh Tabatabai, Christian Senft, Peter Hau, Michael Sabel, Ulrich Herrlinger, Ralf Ketter, Uwe S. Schlegel, Christine Marosi, Guido Reifenberger, Wolfgang Wick, Joerg Tonn, Hans-Georg Wirsching; Department of Neurosurgery LMU, Munich, Germany; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; University of Tübingen, Tübingen, Germany; Department of Neurosurgery, Goethe University Frankfurt, Frankfurt, Germany; University of Regensburg, Regensburg, Germany; Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany; University of Bonn, Bonn, Germany; Department of Neurosurgery, University Hospital Homburg, Homburg, Germany; Knappschaftskrankenhaus University Hospital, Bochum, Germany; University of Vienna, Wien, Austria; Institute of Neuropathology, Heinrich-Heine-University, Duesseldorf, Germany; Neurology Clinic, Heidelberg, Germany; Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany

Abstract Disclosures

Abstract: 

Background: The role of surgery for recurrent glioblastoma is under debate. Tumor volume at recurrence was prognostic in single-institution retrospective studies, but no data from prospective multicenter trials for recurrent glioblastoma have been published to date. Here, we report the association with outcome of surgery for recurrent glioblastoma in a well characterized patient cohort treated in the DIRECTOR trial, which evaluated the effect of two different dose-intensified temozolomide regimens at first recurrence of glioblastoma. Methods: We analyzed prospectively collected clinical, molecular and imaging data from the DIRECTOR cohort (N = 105). Imaging data was available from 87 patients. Volumetric analysis was performed based on gadolinium (Gd) enhancement on MRI and correlated with progression-free survival (PFS) and overall survival (OS). Proportional hazard models were applied to obtain prognostic factors. Results: 71 of 105 patients received surgery at recurrence. Prognostic factors were balanced between patients who had undergone surgery and those who had not, including age (P = 0.358), O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation (P = 0.965), isocitrate dehydrogenase (IDH)-1 mutation (P = 0.724), Karnofsky performance score (P = 0.880), or steroid intake before randomization (P = 0.950). Mean tumor volumes in patients who had received surgery were smaller at study entry than in patients who had not undergone surgery (3.0 cm3[range 0-37] versus 6.8 cm3[range 1-23], P < 0.001). The outcomes in patients who did or did not receive surgery at recurrence were similar for PFS (2.0 months [95% CI 3.5-7.1] vs. 1.9 months [95% CI 1.9-6.4], P = 0.1974) and OS (9.2 months [95% CI 8.7-12.6] vs 9.4 months [95% CI 8.3-13.5], P = 0.9538). Among patients who underwent surgery for recurrence, post-surgery imaging was available in 59 cases. In these patients, complete resection of Gd-enhancing tumor (N = 39) versus residual detection of Gd enhancement (N = 20) was associated with improved OS (11.5 months [95% CI 9.3-15.1] vs. 6.7 months [95% CI 5.2-9.5], P = 0.006). Conclusions: Surgery at first recurrence of glioblastoma may improve outcome if complete resection of Gd-enhancing tumor is feasible.

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por cyto às 16:54

Terça-feira, 23.06.15

A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma.

A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Oral Abstract Session, Central Nervous System Tumors
Abstract Number: 

2005

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2005)
Author(s): 
Shiao-Pei S. Weathers, Stan Xiaosi Han, Diane D Liu, Charles A. Conrad, Mark R. Gilbert, Monica Elena Loghin, Barbara Jane O'Brien, Marta Penas-Prado, Vinay K. Puduvalli, Ivo Tremont-Lukats, W. K. Alfred Yung, John Frederick De Groot; The University of Texas MD Anderson Cancer Center, Brain and Spine Center, Houston, TX; Division of Neuro-Oncology, Department of Neurology University of Alabama at Birmingham, Birmingham, AL; The University of Texas MD Anderson Cancer Center, Houston, TX; Neuro-Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX; Ohio State University Comprehensive Cancer Center, Columbus, OH

Abstract Disclosures

Abstract: 

Background: Antiangiogenic therapy can rapidly reduce vascular permeability, but high doses of bevacizumab (BEV) may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose BEV in combination with lomustine (CCNU) compared to standard dose BEV in patients with recurrent glioblastoma. Methods: Eligibility criteria included age > 18 yrs with recurrent glioblastoma after temozolomide chemoradiotherapy. Patients were stratified by age, KPS, 1st/2nd/3rd recurrence, and scheduled surgery and randomized to BEV 5 mg/kg every 3 weeks plus CCNU 90 mg/m2 every 6 weeks or BEV 10 mg/kg every 2 weeks. The primary objective was progression free survival (PFS) with secondary objectives of radiographic response (RR), 6 month progression-free survival (PFS-6), overall survival (OS), time to progression (TTP), and safety. Results: 70 of 82 patients accrued were randomized and 68 were treated from 2010-2014. Median follow-up was 30.5 months. At the time of this analysis, 62 patients had progressed or died. For 68 evaluable patients, median PFS was not significantly longer in the BEV + CCNU arm (4.34 months, CI: 2.96-8.34) compared to the BEV alone arm (4.11 months, CI: 2.69-5.55, p = 0.19). In patients with one recurrence (n = 24 and 23, respectively), there was a trend towards statistical significance in longer median PFS time in the BEV + CCNU arm (4.96 months, CI: 4.17-13.44) compared to the BEV alone arm (3.22 months CI: 2.5-6.01, p = 0.08). Median OS in patients with 1 recurrence on BEV + CCNU was longer (13.05 months, CI: 8-19.17) than those treated with BEV alone (8.79 months, CI: 6.42-20.22, p = 0.77) but this did not reach statistical significance. No unexpected grade 3 or 4 toxicities were observed. The trial was closed early due to futility.Conclusions: The combination of low dose BEV + CCNU is a safe and effective regimen. The study was not designed to test only at first recurrence, but in that subgroup there was a strong trend towards the combination supporting the findings of the recently published BELOB trial.With a larger sample size, a statistically significant difference in median PFS between treatments arms would likely have been observed. Clinical trial information: NCT01067469

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por cyto às 16:52

Terça-feira, 23.06.15

safety and intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with recurrent glioblastoma (GBM).

A phase 2 study on efficacy, safety and intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with recurrent glioblastoma (GBM).

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Poster Session, Central Nervous System Tumors
Abstract Number: 

2044

Poster Board Number: 
Board #33
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2044)
Author(s): 
Ulrik Niels Lassen, Morten Mau-Soerensen, Andrew L. Kung, Patrick Y. Wen, Eudocia Quant Lee, Scott R. Plotkin, Aida Muhic, Tami Rashal, Tony Williams, Dilara McCauley, Joel Ellis, Jean-Richard Saint-Martin, Robert Carlson, Ran Frenkel, Sharon Shacham, Mansoor Raza Mirza, Michael Kauffman, Andrew B. Lassman; Rigshospitalet, Copenhagen, Denmark; University Hospital, Rigshospitalet, Copenhagen, Denmark; Columbia University Medical Center and Herbert Irving Comprehensive Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA; Karyopharm Therapeutics, Inc., Newton, MA; Karyopharm Europe GMBH, Munich, Germany

Abstract Disclosures

Abstract: 

Background: Patients (pts) with recurrent GBM have few treatment options and a poor prognosis. Selinexor is an oral inhibitor of XPO1 mediated nuclear export resulting in nuclear retention of multiple tumor suppressor proteins (TSPs) including p53, pRB, CDKN2A, p21 and FOXO. Mean IC50 of selinexor in pt derived GBM neurosphere cultures was 133 nM. In a pt derived orthotopic murine xenograft model, selinexor demonstrated marked inhibition of tumor growth in vivo and prolonged survival (P= .001). Methods: This study (NCT01986348) is an open label, multicenter, two-arm phase II trial enrolling pts with recurrent GBM after radiation therapy with concurrent and adjuvant temozolomide. Pts in Arm A received 3 doses (50 mg/m2) of selinexor prior to surgery, and resumed selinexor after surgery. Pts in Arm B received selinexor alone (50 mg/m2 BIW) until disease progression. Results: (Jan 22, 2015) 7 pts (6/1 M/F, median age 57, 1–2 prior treatment regimens) were treated on Arm A and 15 pts (11/4, M/F, median age 62; 1–3 prior treatment regimens) were treated on Arm B. Mean plasma PK concentration was 999 nM (311-2071 nM) and mean tumor concentration was 136 nM (40-291 nM) in 6 pts. Grade 1/2 AE’s (Arm B) included thrombocytopenia (27%/27%), anorexia (13%/33%), fatigue (7%/40%), and hyponatremia (47%/0%). One Grade 3 AE was reported in ≥ 2 pts (fatigue) and no Grade 4 AEs were reported. Investigator reported best responses for 12 evaluable pts (Arm B) were: 2 partial responses (17%), 4 stable disease (33%) and 6 progressive disease (50%). Analysis of XPO1 and TSP expression in tumor tissue is ongoing. Conclusions: Oral selinexor at 50 mg/m2 BIW achieves concentrations in GBM tissue exceeding the IC50 in pre-clinical models. Main toxicities are fatigue and anorexia. Partial responses and stable disease were observed. Clinical trial information: NCT01986348

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por cyto às 16:51

Terça-feira, 23.06.15

Continuous low dose temozolamide with or without VT-122 in glioblastoma.

Continuous low dose temozolamide with or without VT-122 in glioblastoma.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
This abstract will not be presented at the 2015 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 

e13010

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr e13010)
Author(s): 
Tanweer Shahid, Gouri Shankar Bhattacharyya, Hemant Malhotra, Kanaka Setty Govindbabu, Purvish M. Parikh, Anantbhushan Ranade, Ghanashyam Biswas, Shailesh Arjun Bondarde, Amitabha Chanda, Newell F. Bascomb; AMRI Hospital, Kolkata, India; Orchid Nursing Home, Kolkata, India; Birla Cancer Center, SMS Medical College Hospital, Jaipur, India; Kidwai Memorial Institute of Oncology, Bangalore, India; Indian Cancer Society and ICON ARO, Mumbai, India; Seth Ramdas Shah Memorial Hospital, Pune, India; Sparsh Hospital and Critical Care, Bhubaneshwar, India; Shatabdi Super Specialty Hospital, Nashik, India; Neuro Surgery, Fortis Hospital, EM Bypass Road,, Kolkata, West Bengal, India; Vicus Therapeutics, Morristown, NJ

Abstract Disclosures

Abstract: 

Background: Recurrent Glioblastoma is associated with poor prognosis despite treatment.Treatment options are limited. One of the novel methods of delivering Temozolomide is to use metronomic dosing which also has anti angiogenic properties, beside cytotoxic properties. Preclinical and clinical studies of beta-blockers and NSAIDs.Propranolol and etodolac (PE) are well known drugs that function by blocking adrenergic and prostaglandin signaling pathways.Their ability to inhibit cancer progression and metastasis may be through Anti-angiogenesis by inhibiting the expression of HIF-1alpha,iNOS and reducing cytokine—driven induction of immune regulating indoleamine 2,3 dioxygenase (IDO).Propranolol and etodolac induce changes in tumor microenvironment and immune system.The aim of this study was to evaluate the impact of the co-administration of the beta blocker Propranolol (P) and the selective COX-2 inhibitor Etodolac (E) on survival of patients with Recurrent Glioblastoma receiving Continuous low dose Temozolomide in metronomic dosing Methods: Eligible patients who had radio-chemotherapy with or without surgery for glioblastoma. All patients were treated with Temozolomide 20mg in empty stomach twice a day continuously. Patients were randomized to VT-122. All patients continued on standard planned supportive care. Patient who had received Temozolomide were continued either till progression or unacceptable toxicity. Results: 41 patients - 24 men and 16 women with proven advanced Recurrent Glioblastoma. Conclusions: Metronomic dosing of Temozolomide with VT-122 is an effective option in treatment of recurrent glioblastoma. The median survival time is almost doubled. Side-effects are manageable.

 Metrionomic
Temozolomide
(n=20)
Metrionomic
Temozolomide
and VT-122 (n=21)
Median Karnofsky Score >60 >60
Response Rate 7 (35%) 12 (57%)
Complete Response 1 (5%) 5 (24%)
Partial Response 4 (20%) 7 (33%)
Stable Disease 3 (15%) 3 (14%)
1 year survival rate 6 (30)% 14 (67%)
Median Overall Survival 9.2 months 17.6 months
Thrombocytopenia Grade III/IV 3 (15%) 5 (24%)
Neutropenia Grade III/IV 1 (5%) 2 (10%)
Anemia Grade III/IV 3 (15%) 6 (29%)

 

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por cyto às 16:50

Terça-feira, 23.06.15

Radiotherapy in relation to temozolomide

Radiotherapy in relation to temozolomide: Subgroup analysis of molecular markers of the randomized phase III study by the EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033) in patients with a high risk low-grade glioma.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Oral Abstract Session, Central Nervous System Tumors
Abstract Number: 

2006

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2006)
Author(s): 
Brigitta G. Baumert, Monika E. Hegi, Warren P. Mason, Gail Ryan, Khê Hoang-Xuan, Jacoline E Bromberg, Martin J. Van Den Bent, Mohamed Ben Hassel, Christine Marosi, Alba Ariela Brandes, Jeremy Rees, Andreas von Deimling, Christian Hartmann, Johan M Kros, Denis A. Lacombe, Thierry Gorlia, David Capper, Sebastian Kurscheid, Roger Stupp; University of Bonn Medical Centre, Bonn, Germany; University of Lausanne Hospitals, Lausanne, Switzerland; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; APHP-CHU Pitié-Salpêtrière, Paris, France; Erasmus MC, Rotterdam, Netherlands; Daniel den Hoed Cancer Center, Rotterdam, Netherlands; Departments of Medical Oncology and Radiotherapy, Centre Eugène Marquis, Rennes, France; University of Vienna, Wien, Austria; Department of Medical Oncology, Azienda USL, Bologna, Italy; National Hospital for Neurology and Neurosurgery, London, United Kingdom; Institute of Pathology, Dept Neuropathology, University of Heidelberg, INF 224, and CCU Neuropathology German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neuropathology, Institute of Pathology, Medizinische Hochschule, Hannover, Germany; Department of Neuropathology, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, Netherlands; EORTC, Bruxelles, Belgium; European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany; Laboratory of Brain Tumor Biology and Genetics, Dept. Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland; University Hospital Zurich & University of Zurich, Zurich, Switzerland

Abstract Disclosures

Abstract: 

Background: A subgroup analysis based on molecular markers of patients randomized between standard radiotherapy (RT) and temozolomide (TMZ) alone in the randomized EORTC22033 trial. Methods: A posthoc analysis of molecular markers was done for 407 patients (of 477 randomized). The IDH status was determined by immunohistochemistry for the most common IDH mutant, complemented by sequencing of IDH1 and 2 for all negative cases. The status of 1p/19q codeletion was evaluated by LOH or FISH, the MGMTpromoter methylation status on the HM450k beadchip (Illumina) and classified by MGMTSTP27. Results: IDH1 and IDH2 mutations were detected in 83% (327/392) and 2.8% (n = 9). Co-deletions of 1p/19q were identified in 33% (n = 117/357). MGMT was methylated in 90% (135/150), of which 86% were IDH mutant (128/140). For 318 patients the status for both IDH1/2 and 1p/19q codel was available: 269 (85%) were IDHmt, 104 (39%) IDHmt/codel and 49 (15%) IDHwt. Mutation of the IDH 1 or 2 (IDHmt) regardless of 1p/19q co-deletion was a positive prognostic factor. Exploratory analysis of these 318 patients showed that patients with IDHmt/non-codel tumors had a shorter PFS after treatment with TMZ than after RT (HR 1.86; 95% CI, 1.21-2.87; logrank p = 0.0043), while no difference was observed between these treatments for patients with IDHwt, and IDHmt/codel tumors. Conclusions: Subgroup analysis suggests that PFS is longer in patients with IDHmut/non-codel tumors when treated in first-line with RT compared to treatment with TMZ. With still only a few events no such difference is visible in 1p/19q co-deleted tumors. However, maturation of survival data is needed to derive more firm conclusions. Clinical trial information: NCT00182819

TreatmentProgression-free survival
PatientsObserved
Events
HR
(95% CI)
P-ValueMedian (95% CI)
(Mths)
RT-IDHmt/codel 45 17 1.00 0.0000 61.6 (42.3, N)
RT-IDHwt 29 25 5.4 (2.9, 10.1) 0.0000 19.1 (11.3, 25.7)
RT- IDHmt/non-codel 89 37 1.1 (0.6, 2.0) 0.6655 55.4 (47.9, 65.9)
TMZ-IDHmt/codel 59 24 1.1 (0.6, 1.9) 0.8509 55.0 (37.9, N)
TMZ-IDHwt 20 15 3.1 (1.6, 6.3) 0.0013 23.7 (5.6, 42.3)
TMZ-IDHmt/non-codel 76 47 2.1 (1.2, 3.6) 0.0103 36.0 (28.4, 46.9)

 

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por cyto às 16:48

Terça-feira, 23.06.15

A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma—First report of the full dataset of the EF14 randomized phase III trial.

Tumor treating fields (TTFields): A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma—First report of the full dataset of the EF14 randomized phase III trial.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Oral Abstract Session, Central Nervous System Tumors
Abstract Number: 

2000

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2000)
Author(s): 
Roger Stupp, Sophie Taillibert, Andrew Kanner, Santosh Kesari, Steven A Toms, Gene H. Barnett, Karen L. Fink, Antonio Silvani, Frank S. Lieberman, Jay-Jiguang Zhu, Lynne Patricia Taylor, Jerôme Honnorat, Andreas Hottinger, Thomas Chen, David Dinh Tran, Chae-yong Kim, Hal W. Hirte, Monika E. Hegi, Yoram Palti, Zvi Ram; University Hospital Zurich & University of Zurich, Zurich, Switzerland; Hopital Pitie-Salpetriere, Paris, France; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; UC San Diego, La Jolla, CA; Geisinger Health System, Danville, PA; Cleveland Clinic Foundation, Cleveland, OH; Baylor Research Institute, Dallas, TX; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; University of Pittsburgh, Pittsburgh, PA; The University of Texas Medical School at Houston, Houston, TX; Tufts Medical Center, Boston, MA; Hopital Pierre Wertheimer, Lyon, France; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; University of Southern California, Los Angeles, CA; Washington University, St Louis, MO; Seoul Natl Univ Bundang Hosp, Seongnam-si, Korea South; Juravinski Cancer Centre, Hamilton, ON, Canada; University of Lausanne Hospitals, Lausanne, Switzerland; Novocure, Haifa, Israel; Tel Aviv University, Tel Aviv, Israel

Abstract Disclosures

Abstract: 

Background: TTFields is an established antimitotic treatment modality delivered to patients by a portable, home use, medical device. Here we evaluate whether this antimitotic effect can be translated into improved survival in a clinical setting. Based on a pre-specified interim analysis on 315 patients, the IDMC recommended early trial closure; we here report the first analysis of the full dataset of 700 randomized patients. Methods: This prospective phase 3 trial randomized patients with newly diagnosed glioblastoma, after completion of concomitant chemoradiotherapy, to receive either adjuvant temozolomide (TMZ) chemotherapy alone, or TMZ with TTFields (TTF/TMZ). The primary endpoint was progression-free survival, with overall survival, safety, cognitive function and quality of life as secondary endpoints. Results: (ITT) From 2009 to 2014, 700 Grade IV astrocytoma (glioblastoma) patients (68% male) were randomized 2:1. Patient characteristics were well balanced: median age was 56 and 57 years in the TMZ and TTF/TMZ arms, respectively. Tumor was resected in 87% of patients. MGMT was centrally assessed in 77% of patients, 35% and 39% of the tumors had a methylated promoter; 10% and 8% of the results were invalid. Median time from diagnosis to randomization was 3.8 and 3.7 months. Progression-free survival was 7.1 for TTF/TMZ vs 4.2 months for TMZ alone, hazard ratio (HR) 0.694 (95% CI 0.558-0.863) log rank p = 0.0010; overall survival 19.4 vs 16.6 months, HR 0.754 (0.595-0.955), p = 0.0222. This translates into 2-year survival rates of 43% (CI 36-50%) vs. 29% (CI 21-38%). No significant added toxicity was seen in the TMZ/TTF arm. Quality of life and gross cognitive function were comparable in the 2 arms. Conclusions: This is the first randomized trial demonstrating improved progression-free and overall survival of patients treated with Tumor Treating Fields. It sets a new standard of care for patients with glioblastoma, and warrants further investigation in other clinical indications. Clinical trial information: NCT00916409

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por cyto às 16:47


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