Frontline treatment with osimertinib and platinum-based chemotherapy appears safe and effective in patients with EGFR-mutated, advanced, non-squamous non-small cell lung cancer (NSCLC), according to results from the OPAL trial published in the European Journal of Cancer.

In this phase 2 trial, osimertinib was combined with pemetrexed and either cisplatin or carboplatin. Both combinations produced high response rates and progression-free survival (PFS) rates. 

In fact, the combinations produced the highest response rates and longest PFS ever reported in studies of EGFR tyrosine kinase inhibitors in this patient population, according to the researchers.

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The study enrolled 66 patients with previously untreated, EGFR-mutated, advanced non-squamous NSCLC. At baseline, the patients’ median age was 67 years (range, 26-75), 64.2% were women, 98.5% had adenocarcinoma, 32.8% had central nervous system metastasis, and 52.2% had an L858R mutation.

The patients received osimertinib and pemetrexed in combination with either cisplatin (n=33) or carboplatin (n=33) for 4 cycles. All patients also received osimertinib and pemetrexed maintenance until disease progression or discontinuation.

The median follow-up was 33.4 months. The objective response rate was 90.9% in the overall cohort and 90.9% in each arm. The complete response rate was 3% overall, 6.1% in the carboplatin arm, and 0% in the cisplatin arm.

The median PFS was 31 months overall, 29.5 months in the cisplatin arm, and not reached in the carboplatin arm. The 12-month PFS rate was 90.4% overall, 86.9% in the cisplatin arm, and 93.7% in the carboplatin arm. The 24-month PFS rate was 71.8%, 60.1%, and 83.6%, respectively. 

The median overall survival (OS) was not reached in the overall cohort or in either arm. The 12-month OS rate was 96.9% overall, 96.9% in the cisplatin arm, and 97.0% in the carboplatin arm. The 24-month OS rate was 92.3%, 87.5%, and 97.0%, respectively.

Grade 3-4 adverse events that were more common in the carboplatin arm than in the cisplatin arm were neutropenia (60.6% vs 29.4%), anemia (30.3% vs 14.7%), and thrombocytopenia (42.4% vs 0%).

Treatment discontinuation due to adverse events occurred in 14.9% of patients in the cisplatin arm and 12.1% of those in the carboplatin arm. There were no treatment-related deaths in either arm.

“This is the first study to show that OPP [osimertinib and platinum-based chemotherapy] has excellent efficacy with acceptable toxicity in previously untreated EGFR-mutated advanced non-squamous NSCLC patients,” the researchers concluded.

Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


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 1, 2023. doi:10.1016/j.ejca.2023.02.023