Quadruple therapy of chemoimmunotherapy combined with antiangiogenic agent prolongs progression-free survival in EGFR- or ALK-mutated NSCLC progressing on TKIs

The ATTLAS phase III clinical trial enrolled 228 patients with advanced EGFR- or ALK-mutated NSCLC who had received at least one prior EGFR- or ALK TKI. Patients were randomly assigned to receive either quadruple therapy or chemotherapy. The quadruple therapy comprised the following drugs: atezolizumab, bevacizumab, paclitaxel, and carboplatin (ABCP).

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The study results revealed that the median PFS for the ABCP group was 8.48 months, compared to 5.62 months for the chemotherapy group (hazard ratio: 0.62, 95% CI: 0.45-0.86; p = 0.004). Notably, subgroup analyses suggested that PFS was correlated with PD-L1 expression, with hazard ratios of 0.47, 0.41, and 0.24 reported for patients with PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Furthermore, the objective response rate (ORR) for the ABCP group was 69.5%, compared to 41.9% for the chemotherapy group. 

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The results of this clinical trial mark ABCP as the first positive phase III trial with quadruple therapy, suggesting its effectiveness as a treatment option for patients with EGFR- or ALK-mutated NSCLC progressing on TKIs. Quadruple therapy significantly prolonged patients' PFS and improved their response rates.

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Reference: J Clin Oncol. 2023 Oct 20:JCO2301891

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