Outcomes of concurrent versus sequential icotinib therapy and chemotherapy in advanced non-small cell lung cancer with sensitive EGFR mutations

Abstract

To explore a better treatment strategy for patients with advanced non-small cell lung cancer harboring sensitive epidermal growth factor receptor mutations, a total of 271 patients were retrospectively analyzed. The patients were divided into two groups: the combination group (58 cases), which received concurrent icotinib, pemetrexed, and platinum treatment, and the sequential group (213 cases), which received the sequential pemetrexed and platinum therapy, followed by icotinib treatment. The primary end points were progression-free survival (PFS) and PFS on the subsequent line of therapy (PFS2). PFS in the combination group was significantly higher compared with that in the sequential group (16.89 months vs. 9.90 months; p < 0.001). PFS in the combination group was also significantly higher than PFS2 in the sequential group (16.89 months vs. 14.05 months; p = 0.009). The overall survival (OS) of the patients was 33.22 months (95% confidence interval (CI): 26.99-37.01) in the combination group and 26.47 months (95% CI: 25.05-26.95) in the sequential group (p < 0.001). The combination group's objective response rate was superior to that of the sequential group (79.31% vs. 52.11%; p < 0.001). Propensity score matching also revealed that icotinib therapy combined with chemotherapy extended the PFS, PFS2, and OS of the patients (p < 0.0001, p = 0.003, and p = 0.001, respectively). The combination group's objective response rate was also better compared with the sequential group (79.31% vs. 51.72%; p = 0.001). In conclusion, our study demonstrated icotinib combined with chemotherapy can improve survival efficacy better than the separated two-line therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? For advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutants, EGFR-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment. Unfortunately, most patients with NSCLC harboring EGFR mutations acquire EGFR-TKI resistance after EGFR-TKI treatment for about 10-14 months. Studies have indicated that chemotherapy plus EGFR-TKIs may have combined effects on the growth of NSCLC cells. However, until now, there has been no study comparing the concurrent and sequential EGFR-TKIs plus chemotherapy. WHAT QUESTION DID THIS STUDY ADDRESS? We retrospectively analyzed the efficacy and safety of concurrent versus sequential icotinib and chemotherapy in untreated NSCLC with sensitive EGFR mutations. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? In the patients with NSCLC with sensitive EGFR mutations, the first-line pemetrexed plus platinum combined with icotinib better improved PFS, PFS2, and objective response rate compared with first-line icotinib and second-line pemetrexed plus platinum. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The results of this paper provide guidance for the strategy choice in the treatment of patients with NSCLC.