Durvalumab May Be Effective in Patients with EGFR⁺/ALK⁺ NSCLC

Immune checkpoint inhibitors have improved outcomes and become the standard of care for patients with non–small cell lung cancer (NSCLC) lacking EGFR or ALK alterations (EGFR⁻/ALK⁻). However, their efficacy has not been determined in patients with EGFR⁺/ALK⁺ tumors. In the open-label, phase II ATLANTIC trial, Garassino and colleagues evaluated the safety and efficacy of the anti–PD-L1 antibody durvalumab in 444 patients with heavily pretreated advanced NSCLC in three cohorts of patients defined by EGFR/ALK status and tumor expression of PD-L1. Cohort 1 had 111 patients with EGFR⁺/ALK⁺ NSCLC, cohort 2 had 265 patients with EGFR⁻/ALK⁻ NSCLC, and cohort 3 had 68 patients with EGFR⁻/ALK⁻ NSCLC with at least 90% of tumor cells expressing PD-L1. Cohorts 1 and 2 each included patients with at least 25% of tumor cells expressing PD-L1 and with less than 25% of tumor cells expressing PD-L1. The primary endpoint was objective response in patients with increased PD-L1 expression. Of the patients with increased PD-L1 expression, objective responses were achieved in 9 of 74 patients (12.2%) in cohort 1, 24 of 146 patients (16.4%) in cohort 2, and 21 of 68 patients (30.9%) in cohort 3. Durvalumab had an acceptable tolerability profile, with grade 3–4 treatment-related adverse events occurring in 40 of 444 (9%) patients. Taken together, the results of the phase II ATLANTIC trial indicate that durvalumab has an acceptable tolerability profile and clinical activity in patients with heavily pretreated NSCLC. Responses were observed in patients with EGFR⁻/ALK⁻ and EGFR⁺/ALK⁺ tumors, with higher response rates in tumors with increased PD-L1 expression. These findings support further investigation of durvalumab in patients with EGFR⁺/ALK⁺ tumors.

Garassino MC, Chol BC, Kim JH, Mazières J, Vansteenkiste J, Lena H, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol 2018 Mar 12 [Epub ahead of print].

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