Afatinib seems promising for EGFR-mutated lung cancer

21 Dec 2015

Patients with EGFR-activating mutations in advanced lung cancer seem to benefit more from afatinib than gefitinib as first-line treatment, researchers report.

In the global, randomized, open-label Phase 2b LUX-Lung 7 (LL7) trial (1), the irreversible ErbB family blocker afatinib significantly improved efficacy versus gefitinib across a range of clinically relevant endpoints, such as progression-free survival, time-to-treatment failure and objective response rate. "Based on these results I would consider afatinib as the EGFR tyrosine kinase inhibitor (TKI) of choice for the first-line treatment for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC)," lead author, Professor Keunchil Park, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, said.

NSCLC is the most common type of lung cancer: activating epidermal growth factor receptor (EGFR) gene mutations are more frequently observed in non-smokers and women, and occur in 50% of Asians and only 10% of non-Asians. The targeted agents afatinib and gefitinib block key pathways involved in tumor growth and spread. They have both been approved for the treatment of naive patients, based on the results of Phase 3 trials, confirming their superiority compared to chemotherapy. Unlike the first-generation EGFR inhibitor gefitinib, the irreversible ErbB family blocker afatinib is suggested to be active in prolonging tumor response and delaying disease progression.

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“The improvement became more pronounced over time”

In the first head-to-head LUX-Lung 7 trial, afatinib candidates to be a better choice for EGFR-mutation positive NSCLC naive patients who had received no prior treatment. Interestingly, the improvement in progression-free survival became more pronounced over time with a significantly higher proportion of patients alive and progression-free at 18 months and 24 months, showing a greater long-term benefit of using the irreversible ErbB family blocker afatinib.

In particular, out of the 319 patients who were randomized to afatinib or gefitinib, researchers reported:

  • A significantly higher proportion responded to the first than the second with a median duration of response of 10.1 months and 8.4 months, respectively.
  • First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% versus gefitinib
  • Regarding the tolerability profile, that overall, the frequency of severe adverse events was similar in both arms with slightly different toxicity profiles.
  • The adverse events observed with both treatments were predictable and manageable, leading to an equally low rate of treatment discontinuation in both arms (6.3%).

Patient comorbidities must not be neglected

Dr. Martin Reck, Chief oncology physician at the Department of Thoracic Oncology, Hospital Grosshansdorf, Germany, who was not involved in the study, cautions that the individual patient and his or her comorbidities will still guide the selection of EGFR inhibitor.

 "Following these trial results, afatinib will be one of the most attractive EGFR tyrosine kinase inhibitors. However, tolerability also plays a determining role in the selection and dosing of a tyrosine kinase inhibitor. The tolerability profiles between gefitinib and afatinib are different and the selection of the therapy will still be based on the individual clinical decision," he said.

The primary analysis of overall survival data is planned in 2016 and will provide further responses.

Source: Science Daily

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