Across the ATLANTIC.

Top Line: The PACIFIC trial didn’t require tumor testing of PD-L1, much less EGFR or ALK, so how should we apply its results to our patients with EGFR- and/or ALK-aberrant non-small cell lung cancer (NSCLC)?
The Study: The phase 2 ATLANTIC trial is making slightly less waves than its predecessor, but it adds some important data on the efficacy of durvalumab (anti-PD-L1). All enrollees failed at least two prior therapies including a platinum regimen (plus an EGFR/ALK-targeted agent if aberrant). Patients were assigned in a single arm fashion to receive durvalumab 10 mg/kg q2 weeks for a planned 12 months. Once testing of PD-L1 tumor expression(%) became available, AstraZeneca made a protocol amendment stating only the following three cohorts were eligible for the primary endpoint of objective response (OR): EGFR- and/or ALK-aberrant and ≥25% expression [1], EGFR/ALK wild type and ≥25% [2], and EGFR/ALK wild type and ≥90% [3]. OR rates among the 288 of 444 enrollees eligible for this analysis were 12%, 16%, and 31%, respectively. The rate of grade 3-4 toxicity among all 444 patients treated was 9%, most commonly pneumonitis. While results are similar to the phase 2 KEYNOTE-001 (pembro) and CheckMate-063 (nivo) trials, this is the first study to prospectively establish (albeit underwhelming) efficacy among EGFR/ALK-aberrant NSCLC.
Bottom Line: Durvalumab has some level of efficacy across of all kinds of NSCLC...that is if it has at least 25% tumor expression of PD-L1. But it’s more likely to work on more immunogenic tumors such as those with even higher PD-L1 expression and/or without EGFR/ALK-aberrations.


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