COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib

Background: COMPEL (NCT04765059) was a global, randomized, double-blind study that evaluated osimertinib plus chemotherapy versus placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) following non-central nervous system (CNS) progression on first-line osimertinib. Patients and methods: Patients were randomly assigned to receive osimertinib 80 mg, or placebo, once daily (o.d.) in combination with chemotherapy [cisplatin 75 mg/m² or carboplatin area under the curve 5 plus pemetrexed 500 mg/m² every 3 weeks (q3w) for four cycles], followed by osimertinib 80 mg, or placebo, o.d. in combination with maintenance pemetrexed (500 mg/m² q3w) until progression. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included CNS PFS according to CNS metastases status at baseline and overall survival (OS). Results: Ninety-eight patients were randomly assigned (49 per arm). Median PFS in all patients was 8.4 months [95% confidence interval (CI) 5.7-11.8 months] with osimertinib plus chemotherapy versus 4.4 months (95% CI 3.5-5.6 months) with placebo plus chemotherapy [hazard ratio (HR) 0.43, 95% CI 0.27-0.70]. CNS PFS was longer with osimertinib plus chemotherapy versus placebo plus chemotherapy (HR 0.56, 95% CI 0.27-1.13) in patients without baseline CNS metastases (n = 75). Median OS in all patients was 15.9 months (95% CI 12.4-20.8 months) with osimertinib plus chemotherapy versus 9.8 months (95% CI 8.4-17.2 months) with placebo plus chemotherapy (HR 0.71, 95% CI 0.42-1.23). Grade ≥3 adverse events occurred more frequently with osimertinib plus chemotherapy (63%) than placebo plus chemotherapy (46%). Conclusions: In patients with non-CNS progression on first-line osimertinib, osimertinib plus chemotherapy was associated with improved PFS and longer OS compared with placebo plus chemotherapy. These findings support osimertinib as a backbone treatment for EGFR-mutated advanced NSCLC through lines of therapy.