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Domingo, 14.06.15

Afatinib Active in Certain Uncommon EGFR Mutations

In Lung Cancer, Afatinib Active in Certain Uncommon EGFR Mutations


Afatinib has activity against non-small cell lung carcinoma (NSCLC) tumors that harbor certain uncommon mutations, according to a combined post-hoc analysis published online ahead of print this week in the journal The Lancet Oncology.  

This post-hoc analysis is a combination of a phase 2 trial (LUX-Lung 2) and two phase 3 trials (LUX-Lung 3 and LUX-Lung 6) that looked into tyrosine kinase inhibitor-naive patients with EGFR mutations in advanced NSCLC. The researchers enrolled 600 patients and randomly assigned them to receive afatinib.

Based on the mutation status, the patients were then categorized into group 1 (point mutations or duplications in exons 18–21), group 2 (e-novo Thr790Met mutations in exon 20 alone or in combination with other mutations), or group 3 (exon 20 insertions). The most frequent uncommon mutations, Gly719Xaa, Leu861Gln, and Ser768Ile, were also assessed.  

Out of 75 (12%) patients with uncommon EGFR mutations, the patients in group 1 had an objective response rate of 71.1% (95% CI: 54.1, 84.6), followed by 14.3% (95% CI: 1.8, 42.8) in group 2 and 8.7% (95% CI: 1.1, 28.0) in group 3.

Median progression-free survival was 10.7 months (95% CI: 5.6, 14.7) in group 1, 2.9 months (95% CI: 1.2, 8.3) in group 2 and 2.7 months (95% CI: 1.8, 4.2) in group 3.

Median overall survival was 19.4 months (95% CI: 16.4, 26.9) in group 1, 14.9 months (8.1, 24.9) in group 2, and 9.2 months (4.1, 14.2) in group 3.


RELATED: Results of Nivolumab CheckMate 057 Study May Change Treatment of Lung Cancer

For the most frequent uncommon mutations, 77.8% (95% CI: 52.4, 93.6) of the patients with Gly719Xaa had an objective response, followed by 56.3% (95% CI: 29.9, 80.2) with Leu861Gln, and 100% (95% CI: 63.1, 100.0) with Ser768Ile.

The findings suggest that afatinib is active against most frequent uncommon mutations (Gly719Xaa, Leu861Gln, and Ser768Ile) and ultimately can help clinical decisions for the patients with advanced NSCLC tumors that harbor uncommon EGFR mutations.


  1. Yang C-H, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015. [Epub ahead of print]. doi: 10.1016/S1470-2045(15)00026-1.

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por cyto às 13:18

Domingo, 14.06.15

Blood test detects breast cancer metastasis early

Blood test detects breast cancer metastasis early

Circulating tumor DNA in the blood identified breast cancer metastases an average of 11 months before clinical detection, according to a new study published in EMBO Molecular Medicine (2015; doi:10.15252/emmm.201404913).

Although the chances of a breast cancer cure have increased in recent decades, if metastases occur, the disease remains essentially incurable. One reason for this could be that the metastases are detected late, after they have grown enough to cause symptoms or be seen on a radiological scan. If they could be found sooner, treating the new tumors might be possible. Research findings from Lund University in Sweden now provide new hope for a way of detecting metastases significantly earlier than is currently possible.

The discovery was made by a research team led by Lao Saal, MD, PhD, and is based on what is known as cell-free circulating DNA, which are small fragments of genetic material from different cells that circulate in the blood. It is normal to have low amounts of such DNA material in the blood, but in the case of diseases such as cancer, these amounts can increase. Furthermore, in cancer patients, the circulating DNA contains the genetic mutations that are specific to the tumor.

Lao Saal and his colleagues used previously gathered material from a breast cancer study that has been underway in Lund since 2002. The material contained samples from surgically removed tumors from patients with nonmetastatic disease as well as blood samples taken from the patients at regular intervals during the years in which they were followed up.

The tumor samples contained many genetic changes, which constituted a fingerprint specific to each tumor. Researchers then looked in the blood samples for circulating tumor DNA (ctDNA) with the same fingerprint. Although the study is fairly small and includes material from only 20 women, its results are striking.

"For 19 of the 20 women, the ctDNA in the blood samples gave a clear indication of how things would turn out. The women who never got a relapse had no detectable ctDNA, whereas all women who had tumor DNA in their blood eventually had symptomatic relapses that were diagnosed in the clinic", said Lao Saal.

The metastases were also reflected in the blood samples at an early stage. There it was possible to find signs of the new tumors many months before hospital investigations revealed that the patients had suffered a relapse.

"The circulating tumor DNA values in the blood samples identified the metastases on average 11 months before they were diagnosed by standard clinical procedures. In some cases, the blood test detected the metastasis 3 years earlier. If we could find the cancer recurrences that much earlier, we might be able to treat them more successfully," said Lao Saal.

The study must be followed by investigations with more participants, so that researchers can be sure that the results are sustainable. If they are, ctDNA testing could become a way of detecting breast cancer metastasis much earlier than is currently possible.

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por cyto às 13:16

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Junho 2015