A retrospective analysis of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy for advanced or recurrent non‐small cell lung cancer

Abstract

Background Although clinical trials have investigated the addition of pembrolizumab to chemotherapy for non‐small cell lung cancer, none have investigated the addition of chemotherapy to pembrolizumab. Methods We conducted a retrospective study of 71 NSCLC patients including 33 treated with pembrolizumab plus chemotherapy (combination therapy group) and 38 treated with pembrolizumab monotherapy (monotherapy group) from 1 May 2016 to 31 August 2020. Results Eleven of 33 (33.3%) patients in the combination therapy group and 37 of 38 (97.4%) patients in the monotherapy group had programmed cell death ligand‐1 (PD‐L1) tumor proportion score (TPS) ≥50%. Objective response rate (ORR) and median overall survival (OS) were not significantly different between the combination therapy group and monotherapy group (54.5% vs. 47.4, p = 0.637 and 16.6 vs. 27.0 months, p = 0.463). In patients with PD‐L1 TPS ≥50%, ORR and median OS were not different between the combination therapy group and the monotherapy group (63.6% vs. 48.6%, p = 0.499 and not reached vs. 27.0 months, p = 0.976). Thirty‐three (100%) patients experienced adverse events (AEs) in the combination therapy group and 32 (84.2%) in the monotherapy group. Treatment discontinuation at 1 year due to AEs occurred more frequently in the combination therapy group (45.2%) than in the monotherapy group (21.1%). Conclusion There was no significant difference in ORR and OS between the two groups, and treatment discontinuation was more frequent in the combination group. A randomized controlled trial is needed to evaluate the addition of chemotherapy to pembrolizumab for first‐line treatment in patients with PD‐L1 TPS ≥50%.

Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio

“…In a meta-analysis of four phase III clinical trials, combination therapy demonstrated longer PFS and similar OS compared with pembrolizumab monotherapy. Although the study results favored combination therapy, subsequent real-world studies demonstrated similar PFS and OS among patients who received different treatment modalities [11,12,14]. On the contrary, a multicenter retrospective cohort study conducted by Matsumoto et al showed that pembrolizumab monotherapy provided longer PFS than combination therapy in the subgroup of patients with metastases to the liver, lung, adrenal glands, bone, or lymph nodes [13].…”

“…Recently, cohort studies comparing treatment efficacy of pembrolizumab alone or in combination with chemotherapy have been carried out, but no significant difference in survival outcomes was observed amongst patients who received different treatment modalities [11][12][13][14]. The possible reasons for the insignificant difference might be attributed to the higher toxicities in combination therapy [14] and its limited clinical benefits in certain patient subgroups [11].…”

Real-world outcomes of immunotherapy with or without chemotherapy in first-line treatment of advanced non-small cell lung cancer

“…The reported rates of AEs in mono-IT real-world studies range from the highest being very similar to those observed in our study (86%) and the lowest reporting any AE in only approximately one-third of patients ( 45 ). Chemo-IT real-world studies report AEs occurring in the majority of patients, with severe AEs observed in a wide range of patients, from 18% to 73% ( 60 – 62 ). Thus, although available real-world evidence seems reassuring, with similar or even lower rates of AEs than in RCTs, it should be acknowledged that the data are still very limited and that there is possible underreporting of AEs outside the clinical trial setting ( 45 ).…”

The use of immunotherapy in older patients with advanced non-small cell lung cancer

“…Serum level of albumin lower than 3.5 g/ dL and ECOG PS 2 were negative predictors for survival outcomes [51]. Another small retrospective analysis demonstrated no differences in ORR and OS between 33 patients treated with first-line chemotherapyimmunotherapy combination vs. 38 patients treated with single agent immunotherapy [52].…”