Third-line treatment options remain elusive for advanced, EGFR wild-type NSCLC

By Sarah Pritchard, medwireNews Reporter

Phase II study findings show only marginal positive effects of third-line treatment with afatinib for advanced non-small-cell lung cancer (NSCLC) in patients with wild-type epidermal growth-factor receptor (EGFR) tumour status.

There were no confirmed complete or partial responses, and only a quarter of the cohort achieved disease control, for a median of 19.3 weeks, report the researchers in The Oncologist.

There is currently no standard therapy for this population, the team notes, and while the current findings reveal only limited clinical benefit of afatinib, the fact that there was even marginal benefit “highlights the need to investigate further the opportunities for biomarker-driven therapy in wild-type EGFR patients.”

Keunchil Park, from the Samsung Medical Center in Seoul, Republic of Korea, and co-workers, investigated the efficacy of the irreversible inhibitor of the ErbB receptor family – afatinib – in a group of 38 stage IIIB/IV NSCLC patients aged a median of 58 years who had previously been tested by direct sequencing and found to have wild-type EGFR tumours. All patients had undergone two previous chemotherapy regimens, and all received 40 mg afatinib orally, on a 28-day dosing cycle.

The overall disease control rate was 24%, representing nine patients who had stable disease for at least 6.0 weeks after treatment initiation. No patient achieved a confirmed objective (complete or partial) tumour response. In terms of secondary study endpoints, the median progression-free survival was 4.1 weeks, median overall survival was 31.4 weeks, and after the total median follow-up time for the study (56.2 weeks), 26% of the cohort were still alive.

All patients reported at least one adverse event; however, these were manageable and “consistent with the known safety profile of afatinib” remark Park et al. For example, 88% of patients reported experiencing a rash or acne, 62% experienced diarrhoea, 57% reported stomatitis and 14% of patients underwent afatinib dose reduction because of their adverse events.

The researchers acknowledge that the lack of comparator arm in their analysis restricts the ability to draw conclusions from their results, and that real-time quantitative polymerase chain reaction testing was unable to confirm wild-type EGFR status for all patients in the trial.

“Consequently, the use of a validated test with high sensitivity and specificity is one of the elements to be considered in the clinical setting to give patients the best chance of treatment with a targeted therapy”, they suggest.

The team concludes that in the absence of any established third-line treatment in the study population, the role of afatinib “may warrant further investigation within biomarker- driven or combination strategies.”

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