Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC

Abstract

Objectives: Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switch-maintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy. Methods: Patients with stage IIIB/IV non-squamous NSCLC, !18 years, PS 0-2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL). Results: 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months; p ¼ .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months; p < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42-1.01); p ¼ .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35-0.80; p < .01). There were no significant differences in toxicity or HRQoL between the treatment arms. Conclusion: There was a trend toward prolonged OS and significantly longer PFS from switch-maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression.

Molecular genetic tests in survival factors in patients with NSCLC in the clinical practice of Kazakhstan

“…However, pemetrexed is the drug of choice with proven high efficacy for the first-line therapy in patients with adenocarcinoma. Moreover, modern treatment standards for patients with pulmonary adenocarcinoma also include maintenance therapy with pemetrexed in patients with regression and/or stabilized disease ( 10 , 11 ).…”

“…4. Distribution of NSCLC patients by the number of received courses of antineoplastic pharmacotherapy tients with regression and/or stabilized disease (10,11).…”

Clinical efficacy and safety of pemetrexed with or without either Bevacizumab or Pembrolizumab in patients with metastatic nonsquamous non–small cell carcinoma

“…In the PARAMOUNT trial, for patients who achieved objective response or stable disease after four cycles of pemetrexed‐based doublet, those who went on to receive maintenance pemetrexed have an additional PFS of 1.3 months and OS of 2.9 months when compared with their placebo counterparts 5 . The effectiveness of maintenance pemetrexed in real‐world setting has also been confirmed in multiple randomized controlled trials, 6–11 and also among specific subgroups such as in Japanese population, 12 EGFR mutant patients, 13 and even those with renal impairment 14 …”

Prognostic Value of Post First-Line Chemotherapy Glasgow Prognostic Score in Advanced Non-Small Cell Lung Cancer

“…Thus, in the present study, all patients were analyzed as one cohort. 26 For our main analyses, we included patients who received 3 or 4 courses of carboplatin/vinorelbine if GPS was scored both at baseline and evaluation (main study cohort) (Figure 1). In a sensitivity analysis of B-GPS and survival, we included all patients with a B-GPS, independent of number of completed chemotherapy courses (Figure 1).…”

“…Lung cancer is marked by high inflammation and poor survival, 24,25 and a high proportion of patients have elevated GPS as compared with other cancer types. 25 Therefore, in a randomized phase III trial comparing immediate maintenance pemetrexed with pemetrexed at progression in patients with advanced non-squamous non-small cell lung cancer (NSCLC), 26 we measured B-GPS and E-GPS after induction chemotherapy. The aims were to assess whether E-GPS provides better prognostic information than B-GPS and whether there were associations between response to chemotherapy and B-GPS, E-GPS, or change in GPS.…”