Gefitinib enhances DFS with 10 months compared to platinum-based chemotherapy in EGFR-mutation positive, intermediate-stage non-small cell lung cancer
Cisplatin-based adjuvant chemotherapy is the current standard of care for patients with stage II-IIIA non-small cell lung cancer (NSCLC). Results of a phase III study, presented at ASCO 2017, now showed that targeted therapy with gefitinib appears to be more effective in preventing recurrence than platinum-based chemotherapy in this particular group of patients. In the ADJUVANT study, patients with EGFR-activating mutation, stage II-IIIA NSCLC who received gefitinib after complete resection, remained recurrence free for approximately 10 months longer than patients who received chemotherapy after their resection.
Based on these results, the authors stated that adjuvant gefitinib may ultimately be considered as an important option for stage II-IIIA lung cancer patients with an activating EGFR mutation. Routine EGFR testing should also be considered in this earlier stage of lung cancer, following the recommendation of the researchers.
Due to high chance of recurrence, the five-year survival of patients with stage II-IIIA NSCLC is only 40%. About one fourth of all patients who are diagnosed with NSCLC are eligible for surgery. Amongst that group, about 30% (or 140,000 people worldwide) have an EGFR mutation. Previously, the BR19- and the RADIANT-trials failed to show any benefit of EGFR tyrosine kinase inhibitors in the adjuvant setting for patients with unselected resected NSCLC.
ADJUVANT (NCT01405079) is the first randomized trial to compare gefitinib with vinorelbine+cisplatin (VP) in completely resected, pathological stage II-IIIA (N1-N2) NSCLC with EGFR-activating mutation.
Following surgery, 222 patients who had confirmed activating EGFR mutations in the tumor were randomly assigned to receive gefitinib or chemotherapy (VP). Patients received gefitinib at a dose of 250 mg once daily for 24 months or vinorelbine (25 mg/m2 Day 1 and Day 8) plus cisplatin (75 mg/m2 Day 1) every 3 weeks for 4 cycles. All patients were monitored for disease relapse for about three years. In contrast to BR19 and RADIANT, ADJUVANT did not include stage I patients and only included patients with a confirmed EGFR mutation. The median time to recurrence (disease-free survival [DFS], the primary endpoint of the trial) was 28.7 months for patients who received gefitinib as compared to 18 months for those who received chemotherapy (HR[95%CI]: 0.60[0.42-0.87]; p= 0.005). The 3-year DFS was significantly better with gefitinib at 34.0% versus 27.0% with VP (p= 0.013). There were 76 patient deaths (34.2% of all enrollees) during the trial period; 41 occurred in the gefitinib group and 35 in the chemotherapy group.
Far fewer patients experienced severe side effects with gefitinib (12%) than with chemotherapy (48%). The most common serious side effect in the gefitinib group was elevated liver enzymes, whereas patients in the chemotherapy group had more severe quality of life concerns, including vomiting, nausea, low blood counts, and anemia.
In summary, adjuvant gefitinib significantly prolonged DFS compared with VP in patients with resected stage II-IIIA (N1-N2) NSCLC with EGFR-activating mutation. As such, adjuvant gefitinib should be considered as an option for stage II-IIIA lung cancer patients with an EGFR mutation. As the researchers have a tissue repository from the surgically removed lung tumors, they plan to perform a comprehensive biomarker analysis looking for other potential biomarkers for gefitinib response or resistance, in addition to EGFR.
Wu Y-L, Zhong W, Wang Q, et al. Gefitinib (G) versus vinorelbine+cisplatin (VP) as adjuvant treatment in stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC) with EGFR-activating mutation (ADJUVANT): A randomized, Phase III trial (CTONG 1104). Presented at ASCO 2017; Abstract 8500.