Osimertinib with or without chemotherapy for the treatment of advanced non-small cell lung cancer with EGFR mutations

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI sensitization and EGFR T790M resistance mutations. There is evidence that adding chemotherapy may amplify the benefits of EGFR-TKI therapy.

In this phase 3 international open-label trial, patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (exon 19 deletions or L858R mutations) who had not received prior treatment for advanced disease were randomized in a 1:1 ratio to receive osimertinib (80 mg daily). Once) with chemotherapy (pemetrexed [500 mg/m2 body surface area] and cisplatin [75 mg/m2] or carboplatin [pharmacology-guided dose]) or with osimertinib monotherapy (80 mg/m2) The primary endpoint was investigator-assessed progression-free survival. Response and safety were also assessed.

A total of557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50-63) of patients in the osimertinib-chemotherapy group were alive and 41% (95% CI, 35-47) of patients in the osimertinib group were progression-free. Progression-free survival, as assessed by blinded independent central review, was consistent with the primary analysis (hazard ratio, 0.62; 95% confidence interval, 0.48 to 0.80). Objective (complete or partial) responses were observed in 83% of patients in the osimertinib-chemotherapy group and in 76% of patients in the osimertinib group; the median duration of response was 24.0 months (95% confidence interval, 20.9 to 27.8) and 15.3 months (95% confidence interval, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher in the combination group than in the monotherapy group. This finding was driven by known chemotherapy-related adverse events. The safety profile of osimertinib plus pemetrexed and a platinum drug was consistent with that of the individual drugs.

In advanced non-small cell lung cancer patients with EGFR mutations, first-line treatment with osimertinib plus chemotherapy significantly prolonged progression-free survival compared with osimertinib monotherapy.

OsimertinibThe original drug has been launched in China and has been covered by medical insurance. The price of 80mg*30 tablets per box may be around 5,000 yuan, which is relatively expensive. Currently available overseas Osimertinib generics, such as the specifications produced by Bangladesh Pharmaceutical FactoryThe price of each box of 80mg*30 tablets may be more than 800 yuan (the price may fluctuate due to exchange rates), which is relatively cheap.The ingredients of osimertinib generics are basically the same as the original drug.