Afatinib induces better responses in 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 reported.

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.

Positive clinical outcomes with afatinib

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.

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“Afatinib candidates to be a better choice”

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. “First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% versus gefitinib,” Park said.

Out of the 319 patients who were randomized to afatinib or gefitinib, 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.

“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.”

Similar frequency of adverse events between afatinib and gefitinib

Regarding the tolerability profile, Park said: “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%).”

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. In particular, he commented that:  “the tolerability profiles between gefitinib and afatinib are different and the selection of the therapy will still be based on the individual clinical decision”.

 

Source: eCancer News

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