Non-Small Cell Lung Cancer Coverage from Every Angle

Osimertinib After Progression of Advanced NSCLC Under Study in COMPEL Trial

By: Celeste L. Dixon
Posted: Monday, October 25, 2021

Because of tumor heterogeneity in EGFR-mutated non–small cell lung cancer (NSCLC), it is possible that even when disease has become apparently resistant to osimertinib given in first-line treatment, some cells may remain sensitive to the EGFR tyrosine kinase inhibitor. Instead of discontinuing osimertinib when beginning second-line treatment with platinum-based doublet chemotherapy upon systemic disease progression, as guidelines suggest, continuing it may be beneficial, according to Lecia V. Sequist, MD, MPH, of Dana-Farber/Harvard Cancer Center, and colleagues. This option could “particularly [benefit] patients with central nervous system [CNS] metastases, given [that] osimertinib has demonstrated superior CNS efficacy compared with chemotherapy,” reported Dr. Sequist during the International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer (Abstract P47.11). Additionally, continuing osimertinib might prevent rebound phenomenon, the investigators suggested.

The team has initiated the phase III, double-blind COMPEL trial to test their hypothesis, with accrual of a projected 204 patients underway and results expected in September 2024. Eligible patients are adults with radiologic evidence of non-CNS disease progression following initial response to first-line osimertinib and no evidence of CNS progression.

The patients will be randomly assigned 1:1 across two treatment arms, stratified by the presence or absence of stable CNS metastases, noted Dr. Sequist. Those in arm A will receive the investigator’s choice of pemetrexed plus cisplatin or carboplatin plus osimertinib, followed by pemetrexed maintenance and osimertinib. Patients in arm B will also receive the investigator’s choice of pemetrexed plus cisplatin or carboplatin, but with placebo, followed by pemetrexed maintenance and placebo.

“Patients will receive [their] first treatment dose within 4 weeks of their last first-line osimertinib dose,” said Dr. Sequist. Patients can continue treatment after disease progression provided they benefit, and crossover from placebo to osimertinib will be allowed if disease progression is confined to the CNS, she concluded. 

Disclosure: The study authors reported no conflicts of interest.

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