Post‐progression survival is highly linked to overall survival in patients with non‐small‐cell lung cancer harboring sensitiveEGFRmutations treated with first‐line epidermal growth factor receptor‐tyrosine kinase inhibitors

Abstract

BackgroundIn patients with epidermal growth factor receptor (EGFR)‐mutated advanced non‐small‐cell lung cancer (NSCLC), epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) treatment has shown a good response. Subsequent treatments jeopardize the ability to determine the effect of first‐line chemotherapy on overall survival (OS). Therefore, using patient‐level data, we aimed to study the associations of progression‐free survival (PFS) and post‐progression survival (PPS) with OS after first‐line EGFR‐TKI treatment in patients with EGFR‐mutated NSCLC.MethodsBetween November 2006 and December 2016, we analyzed 92 patients with EGFR‐mutated NSCLC treated with first‐line EGFR‐TKI. The correlations of PFS and PPS with OS were analyzed for each patient.ResultsSpearman's rank correlation and linear regression analyzes showed that PPS correlated highly with OS (r = 0.85, P < 0.05, R 2 = 0.75), whereas PFS correlated weakly with OS (r = 0.76, P < 0.05, R 2 = 0.50). The best responses after first‐line and second‐line treatments were significantly associated with PPS.ConclusionsPPS has a higher impact on OS than PFS in patients with EGFR‐mutated NSCLC treated with first‐line EGFR‐TKIs. These outcomes suggest that the OS in this patient group may be affected by treatments following first‐line chemotherapy; however, this remains to be verified in prospective trials.

Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy

“…The relationship between subsequent treatment after disease progression and OS is intriguing, and previous studies of patient-level data have identified a strong relationship between PPS and OS following first-line treatment for patients with advanced NSCLC or extensivestage small cell lung cancer [12][13][14][15]. However, the correlation between PPS and OS is unclear among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC.…”

“…Thus, pembrolizumab monotherapy is now considered a standard firstline treatment for patients with high PD-L1 expression and no contraindications to immune checkpoint inhibitors. Unfortunately, there are limited patient-level data regarding PPS in this setting [12,15]. Therefore, this study aimed to evaluate the patient-level correlations of PFS and PPS with OS among patients undergoing firstline pembrolizumab monotherapy for advanced NSCLC and how subsequent treatments influence PPS.…”

Post-Progression Survival Is Strongly Associated with Overall Survival in Patients Exhibiting Postoperative Relapse of Non-Small-Cell Lung Cancer Harboring Sensitizing EGFR Mutations

“…Other studies in patients with NSCLC have also demonstrated that PPS is highly correlated with OS beyond first-, second-, or third-line therapy [ 7 , 8 , 39 ]. Moreover, our previous studies revealed that patient-level data on PPS are relevant for evaluating early (first- and second-line) therapies in patients with advanced or metastatic NSCLC, as well as first-line treatment in patients with extensive-disease SCLC [ 10 , 40 , 41 , 42 , 43 ]. Therefore, in this study, we analyzed RFS and PPS in patients with postoperative relapse of EGFR -mutated NSCLC.…”

“…Previously, we reported that PPS has a stronger significance on OS than PFS in patients with NSCLC harboring sensitizing epidermal growth factor receptor ( EGFR ) mutations treated with first-line EGFR-TKIs. This means that treatment beyond disease progression after front-line treatment may have a significant influence on the OS of patients with NSCLC [ 10 ].…”

Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR

“…Along with the new emerging checkpoint inhibitors in lung cancer, it is expected that increasing the overall survival rate in lung cancer will involve detecting particular targetable gene mutations and PD-1/PD-L1 expression. EGFR mutations are linked with good prognosis in lung cancer patients mainly attributed to the treatment of tyrosine kinase inhibitor (TKI) [ 12 ], but also seen in surgically resected non-small cell lung cancer (NSCLC) without receiving TKI [ 13 ]. Several reports have also shown association between the expression of PD-L1 and poor survival rate in lung cancer patients [ 14 , 15 ].…”