Concurrent Osimertinib and Chemotherapy for First-line EGFR-Mutated NSCLC

A phase 2 trial found concurrent osimertinib and platinum-based chemotherapy to be both a safe and effective treatment for previously untreated patients with EGFR-mutated advanced non-squamous non-small cell lung cancer (NSCLC).

“To the best of our knowledge, this is the first prospective study to evaluate the safety and efficacy of a third-generation EGFR-tyrosine kinase inhibitor (TKI) plus platinum doublet chemotherapy in patients with previously untreated EGFR-mutated advanced non-squamous NSCLC,” wrote Ryota Saito, MD, Tohoku University, Sendai, Japan, and colleagues.

The multicenter OPAL study enrolled a total of 67 patients, with 34 patients receiving cisplatin and osimertinib, and 33 patients receiving carboplatin and osimertinib. All patients also received pemetrexed for 4 cycles followed by maintenance therapy with osimertinib and pemetrexed. The primary end points of the trial were safety and objective response rate (ORR), while secondary end points included complete response rate (CRR), disease control rate (DCR), and progression-free survival (PFS).

At the data cutoff date of February 28, 2022, the ORR was 90.9% for all patients. The CRR was 3.0% and the disease control rate was 97.0%. Updated survival data with a median follow-up time of 33.4 months showed the median PFS as 31 months (95% CI, 26.8 months to not reached) and the median overall survival was not reached.

A total of 35 patients (52.2%) discontinued treatment, with 10 patients (14.9%) discontinuing due to adverse events. Grade ≥3 treatment-emergent adverse events were observed in 60 patients (89.6%). The most common grade ≥3 adverse events were decreased neutrophil count, anemia, and decreased platelet count. Neutropenia, anemia, and thrombocytopenia were all more common the carboplatin cohort. Grade ≥3 prolonged QTc was observed in 4 patients in the cisplatin cohort and 4 patients in the carboplatin cohort. While most cases of prolonged QTc were asymptomatic, 1 patient in the carboplatin cohort experienced grade 4 prolonged QTc and grade 3 hypokalemia, resulting in treatment discontinuation.

“The results of the current OPAL study confirm the safety and efficacy of osimertinib plus platinum-based chemotherapy in patients with previously untreated EGFR-mutated advanced non-squamous NSCLC,” concluded Dr Saito et al, leading them to suggest, “the results of the current OPAL study will impact future first-line treatment strategies for EGFR-mutated advanced non-squamous NSCLC.”

Source:

Saito R, Sugawara S, Ko R, et al. Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: The OPAL Study. Eur J Cancer. Published online: March 2, 2023. doi:10.1016/j.ejca.2023.02.023