COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib.
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 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).
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%).
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.
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).
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%).
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.
Authors
Peled Peled, Tufman Tufman, Sequist Sequist, Pasello Pasello, Wang Wang, Antonuzzo Antonuzzo, González Larriba González Larriba, Medina Valdivieso Medina Valdivieso, Cobo Dols Cobo Dols, Milella Milella, Dudnik Dudnik, Martín-Martorell Martín-Martorell, Barneto Aranda Barneto Aranda, Huang Huang, Palicio Palicio, Scimone Scimone, Bria Bria, Servidio Servidio, Pimentel Pimentel, Ganiyu Ganiyu, Zhao Zhao
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