Saltar para: Post [1], Pesquisa e Arquivos [2]

http://cyto.blogs.sapo.pt

Espaço de publicação e discussão sobre oncologia. GBM IMMUNOTHERAPY ONCO-VIRUS ONCOLOGY CANCER CHEMOTHERAPY RADIOTHERAPY



Quarta-feira, 01.07.15

Immunotherapies Shine at ASCO Annual Meeting

Immunotherapies Shine at ASCO Annual Meeting

 

The number of immunotherapy agents approved by the U.S. Food and Drug Administration for the treatment of patients with cancer has risen rapidly in recent years.

Naked monoclonal antibodies, such as bevacizumab, rituximab, and trastuzumab, are now approved for the treatment of various solid and hematologic cancers.

Chemolabeled antibodies, such as brentuximab vedotin, ado-trastuzumab emtansine, and the prostate cancer vaccine sipuleucel-T, add to the growing number of immunotherapies being used to combat cancer.

Positive results from various studies evaluating the use of  standard immunotherapies for different cancers and novel immunotherapies were announced at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL.

The antiangiogenic drug bevacizumab (Avastin), which is already approved for the treatment of six cancer types, was shown to significantly increase progression-free survival (PFS) in combination with carboplatin and paclitaxel in recurrent endometrial cancer compared with carboplatin plus paclitaxel alone.

The phase 2 study showed that the addition of bevacizumab improved median  PFS by more than 4 months.1 A phase 3 trial evaluating the addition of bevacizumab to letrozole as first-line endocrine therapy found that bevacizumab improved PFS by 4 months in patients with hormone receptor-positive advanced breast cancer.2

In addition, BCD-021, a bevacizumab biosimilar candidate was found to be non-inferior to Avastin in patients with non-small cell lung cancer (NSCLC) in a phase 3 trial.3 Biosimilar drugs, unlike generic drugs, do not have identical active ingredients, but are similar.

Ramucirumab (Cyramza), which is now approved for the treatment of patients with gastric, colorectal, and NSCLC, was shown to provide clinical benefit in combination with docetaxel in advanced NSCLC in the phase 3 REVEL trial, but the study had a limited number of East Asian patients who received the docetaxel 75 mg/m2 dose.

A similar phase 2 study in Japanese patients demonstrated improved clinical benefit with ramucirumab plus docetaxel 60 mg/m2 compared with docetaxel plus placebo.4

The addition of obinutuzumab (Gazyva), a CD20-directed cytolytic antibody, to bendamustine was shown to significantly improve PFS compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma (NHL).5

RELATED: Pembrolizumab Immunotherapy Effective in Recurrent, Metastatic Head and Neck Cancer

“Obinutuzumab plus bendamustine followed by obinutuzumab maintenance represents an effective treatment option for patients with relapsed/refractory indolent NHL who are refractory to rituximab,” said Laurie Sehn, MD, MDCM, MPH, of the British Columbia Cancer Agency in Canada.

“The trial results are remarkable as this does represent the first randomized, controlled trial data that demonstrates the utility of a novel anti-CD20 monoclonal antibody in patients with rituximab-refractory lymphoma.”

The results of two trials evaluating combination immunotherapy in patients with advanced melanoma were announced at the conference. One trial included treatment with nivolumab plus ipilimumab and the other with pembrolizumab plus low-dose ipilimumab.

The first study found that nivolumab plus ipilimumab and nivolumab alone had superior clinical activity compared with ipilimumab alone in treatment-naïve patients.6

The second study demonstrated significantly improved PFS and objective response rate (ORR) with nivolumab plus ipilimumab versus ipilimumab alone.7

A small phase 1 study showed an acceptable safety profile with pembrolizumab plus low-dose ipilimumab in patients with advanced melanoma or renal cell carcinoma, as well.8

Immunotherapies for melanoma have multiplied in the last 5 years with the approval of ipilimumab (Yervoy), pembrolizumab (Keytruda), and nivolumab (Opdivo); however, these treatments can cost up to tens of thousands of dollars.

Two new immunotherapies currently under investigation were shown to have encouraging results in patients with relapsed/refractory hematologic cancers.

The first, polatuzumab vedotin, an anti-CD79b antibody-drug conjugate demonstrated high ORRs when used in combination with rituximab in patients with relapsed/refractory follicular lymphoma.9

The other, elotuzumab, was shown to significantly reduce the risk of progression and death when used in combination with lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma.10.

“Elotuzumab now is the first monoclonal antibody demonstrating [PFS] benefit in combination with [lenalidomide/dexamethasone] in a large randomized phase 3 trial of relapsed/refractory multiple myeloma,” said Sagar Lonial, MD, Chief Medical Officer at Winship Cancer Institute of Emory University in Atlanta, GA.

While a number of studies evaluated the use of monoclonal antibodies, there were also various studies presented that tested vaccines and chimeric antigen receptor (CAR) modified T cells.

An autologous tumor-derived heat shock protein peptide vaccine improved survival compared with standard therapy in 46 patients with newly diagnosed glioblastoma multifome, a type of brain cancer that has limited treatment options and poor survival.11

 

RELATED: Older Adults with Head and Neck Cancers May Need More Cautious Treatment Strategies

Two studies assessing the impact of CAR T cells in patients with relapsed/refractory acute lymphocytic leukemia and two forms of NHL found that the immunotherapy induced a high complete response rate and durable response, respectively.12,13

It is clear that the use of immunotherapy for the treatment of cancer is expanding. As FDA-approved biologics demonstrate efficacy in other cancer types and new biologics are displaying efficacy in combination with other biologics and chemotherapy, the role of immunotherapeutic agents for patients with cancer continues to grow.

References

  1. Lorusso D, Ferrandina G, Colombo N, et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: the MITO END-2 trial.  J Clin Oncol. 2015;33(suppl; abstr 5502).
  2. Dickler MN, Barry WT, Cirrincione CT, et al. Phase III trial evaluating the addition of bevacizumab to letrozole as first-line endocrine therapy for treatment of hormone-receptor positive advanced breast cancer: CALGB 40503 (Alliance).  J Clin Oncol. 2015;33(suppl; abstr 501).
  3. Filon O, Orlov S, Burdaeva O, et al. Efficacy and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin: results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC.  J Clin Oncol. 2015;33(suppl; abstr 8057).
  4. Hosomi Y, Yoh K, Kasahara K, et al. Docetaxel + ramucirumab (DR) versus docetaxel + placebo (D) as second-line treatment for advanced non-small cell lung cancer (NSCLC): a randomized, phase II, double-blind, multicenter trial in Japan. J Clin Oncol. 2015;33(suppl; abstr 8054).
  5. Sehn LH, Chua NS, Mayer J, et al. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol. 2015;33(suppl; abstr LBA8502).
  6. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naïve patients with advanced melanoma (CheckMate 067). J Clin Oncol. 2015;33(suppl; abstr LBA1).
  7. Hodi FS, Postow MA, Chesney JA, et al. Clinical response, progression-free survival, and safety in patients with advanced melanoma receiving nivolumab combined with ipilimumab versus IPI monotherapy in CheckMate 069 study. J Clin Oncol. 2015;33(suppl; abstr 9004).
  8. Pembrolizumab (MK-3475) plus low-dose ipilimumab in patients with advanced melanoma or renal cell carcinoma: data from the KEYNOTE-029 phase I study. J Clin Oncol. 2015;33(suppl; abstr 3009).
  9. Advani RH, Flinn I, Sharman JP, et al. Two doses of polatuzumab vedotin in patients with relapsed/refractory follicular lymphoma: durable responses at lower dose level. J Clin Oncol. 2015;33(suppl; abstr 8503).
  10. Lonial S, Dimopoulos MA, Palumbo A, et al. ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide/dexamethasone with/without elotuzumab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2015;33(suppl; abstr 8508).
  11. Bloch O, Raizer JJ, Lim M, et al. Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy. J Clin Oncol. 2015;33(suppl; abstr 2011).
  12. Park JH, Riviere I, Wang X, et al. Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL. J Clin Oncol. 2015;33(suppl; abstr 7010).
  13. Schuster SJ, Svoboda J, Nasta S, et al. Phase IIa trial of chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas.J Clin Oncol. 2015;33(suppl; abstr 8516).

Autoria e outros dados (tags, etc)

por cyto às 11:40



Mais sobre mim

foto do autor


Subscrever por e-mail

A subscrição é anónima e gera, no máximo, um e-mail por dia.

Pesquisar

Pesquisar no Blog  

calendário

Julho 2015

D S T Q Q S S
1234
567891011
12131415161718
19202122232425
262728293031