Continuing Osimertinib in the 2L Treatment Setting: Data From COMPEL

The conversation shifted to the critical issue of treatment sequencing, focusing on how first-line choices influence second-line options. This is especially relevant for patients with EGFR-mutated lung cancer, where options likesuch as chemotherapy, tyrosine kinase inhibitors (TKIs), and amivantamab (Mab) all have roles to play. One study that sparked interest was the COMPEL trial, which evaluated whether continuing a TKI alongside chemotherapy after progression on first-line osimertinib would improve outcomes. Although it enrolled fewer patients than planned and lacked statistical rigor, it suggested a progression-free survival (PFS) improvement from 4.4 to 8.8 months with TKI continuation. Intracranial control was also better, and brain metastases occurred less frequently in the combo arm. This data reopens the question of whether to continue targeted therapy with chemotherapy or switch completely to other modalities.

Opinions on COMPEL’s clinical relevance varied. Some clinicians found the data compelling, as it contrasts with earlier studies likesuch as IMPRESS that showed no benefit from TKI continuation with chemotherapy. The idea that combining targeted agents with chemotherapy could improve outcomes, especially central nervous system (CNS) control, is appealing, but the study’s small size limits strong conclusions. Others approached it cautiously, noting that while the study shows no harm from continuation, it lacks the statistical strength to definitively prove superiority. Real-world decisions often hinge on patient specifics, such as brain metastasis status and prior treatment response.

In this evolving landscape, MARIPOSA-2—a larger, more robust trial assessing chemotherapy plus amivantamab—offers a stronger evidence base for second-line strategies. For some patients with well-controlled CNS disease on TKIs but systemic progression, continuing TKIs with chemotherapy may still make sense. However, newer options likesuch as amivantamab combined with chemotherapy provide promising alternatives. Ultimately, treatment sequencing remains nuanced, balancing evolving data, individual patient characteristics, and drug accessibility to optimize outcomes.