Clinical Impact of Post-Progression Survival on Overall Survival in Elderly Patients with Non-Small-Cell Lung Cancer Harboring Sensitive EGFR Mutations Treated with First-Line EGFR Tyrosine Kinase Inhibitors

Abstract

Background/Aims: More than 50% of patients with lung cancer are aged > 65 years, and non-small-cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer among both elderly and adult patients. Subsequent therapies confound the capability to discern the effect of first-line chemotherapy on overall survival (OS). Therefore, using individual-level data, our study aimed to determine the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS after first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. Methods: Between April 2008 and December 2015, we analyzed 68 elderly patients with NSCLC harboring sensitive EGFR mutations and treated with first-line EGFR-TKI. The relationships of PFS and PPS with OS were analyzed at an individual level. Results: Linear regression analysis showed that PPS was more closely associated with OS (R² = 0.54) than PFS was (R² = 0.48). Best response at first-line treatment, performance status at the end of first-line treatment, and administration of EGFR-TKI rechallenge were significantly correlated with PPS. Conclusions: PPS has a stronger impact on OS than PFS does in elderly patients with NSCLC harboring sensitive EGFR mutations and treated with first-line EGFR-TKI. These results indicate that OS in this patient population may be influenced by treatments subsequent to first-line chemotherapy; however, this remains to be verified in prospective studies.

Post‐progression survival after atezolizumab plus carboplatin and etoposide as first‐line chemotherapy in small cell lung cancer has a significant impact on overall survival

“…11 Several studies found that PPS following first-line chemotherapy for advanced NSCLC at the clinical trial level is strongly correlated with OS; 14,15 similar studies examined the impact of PPS in ED-SCLC and advanced NSCLC based on individual patient-level analysis of the strong correlation between OS and PPS. [16][17][18][19]28,29 In contrast to the previous reports, 26,27 we found that PFS does not necessarily reflect OS in patients with ED-SCLC treated with AteCE, but rather that PPS strongly influences OS. The results show that PFS is shorter than PPS, PPS influences OS intimately, and the relationship is linear.…”

“… 11 Several studies found that PPS following first‐line chemotherapy for advanced NSCLC at the clinical trial level is strongly correlated with OS 14 , 15 similar studies examined the impact of PPS in ED‐SCLC and advanced NSCLC based on individual patient‐level analysis of the strong correlation between OS and PPS. 16 , 17 , 18 , 19 , 28 , 29 …”

“…In non‐small‐cell lung cancer (NSCLC), prolonged PFS does not necessarily translate to prolonged OS, 13 but post‐progression survival (PPS) is highly correlated with OS beyond first‐line treatment 14,15 . Several studies with individual‐level analysis have reported that PPS after first‐line treatment is strongly correlated with OS in metastatic NSCLC 16–18 . Moreover, OS is represented by the summation of PFS and PPS 11 .…”

“… 14 , 15 Several studies with individual‐level analysis have reported that PPS after first‐line treatment is strongly correlated with OS in metastatic NSCLC. 16 , 17 , 18 Moreover, OS is represented by the summation of PFS and PPS. 11 A strong correlation between PPS and OS following treatment with carboplatin and etoposide as first‐line chemotherapy for patients with ED‐SCLC has been previously reported based on individual‐level data.…”