Anti-PD-1 Therapy plus Chemotherapy and/or Bevacizumab as Second Line or later Treatment for Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Immune checkpoint inhibitor combination therapy exhibited outstanding efficacy in first line setting for advanced non-small cell lung cancer (aNSCLC) patients. However, whether PD-1 inhibitor combined treatment is effective in second line or later setting remains unknown. Therefore, we retrospectively evaluated the efficacy of combined therapy of PD-1 inhibitor with chemotherapy and/or bevacizumab compared to PD-1 inhibitor alone for aNSCLC patients in second line or later setting. Patients with aNSCLC who have received anti-PD-1 based therapy between 2015 and 2017 were screened, and 55 patients were ultimately included and divided into the monotherapy group (N=33) and the combination group (N=22). Patients treated with combination therapy exhibited superior PFS versus those treated with monotherapy (median PFS, 7.5 months vs 3.3 months; hazard ratio 0.28; 95% CI, 0.14-0.56; P＜0.001). Objective response rate and disease control rate were 31.8% (7/22) and 95.5% (21/22) in the combination group and 10.0% (3/30) and 46.7% (14/30) in the monotherapy group, respectively (ORR, P=0.075; DCR, P<0.001). Five patients (22.7%) experienced grade 3-4 adverse events in the combination group and two patients (6.1%) in the monotherapy group. Taken together, our results indicated that for NSCLC patients who had failed on the first-line or later treatment, PD-1 inhibitor in combination with chemotherapy and/or bevacizumab might be a favorable treatment option. These findings warrant further validation in prospective studies.

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer

“…In our study, the PFS of the monotherapy group was longer than that of the combination therapy group, which was different from the result of a prior retrospective analysis that compared the efficacy of a PD-1 inhibitor plus chemotherapy and/or bevacizumab and PD-1 inhibitor alone for patients with advanced NSCLC in second-line or later therapy (25). The mPFS was reported at 7.5 and 3.3 months in the combination therapy and monotherapy groups, respectively (P < 0.001).…”

ctDNA Concentration, MIKI67 Mutations and Hyper-Progressive Disease Related Gene Mutations Are Prognostic Markers for Camrelizumab and Apatinib Combined Multiline Treatment in Advanced NSCLC

“…Therefore, we tried to link the PD-L1 expression from primary tumor with the response of 2nd–6th lines therapy to see if we can identify any correlation, while no significant correlation was found, as shown in Supplementary Figure S1 . Another concern is that due to the better response in patients with combined therapy, the effect of stratification by PD-L1 may not be significant anymore, and patients with negative PD-L1 expression may also benefit from the therapy, which was reflected in some recent studies ( 15 – 17 ).…”

“…The combination of Atezolizumab with Bevacizumab, Carboplatin, and Paclitaxel (ABCP) had significantly improved OS (19.2 months vs. 14.7 months) and PFS (8.3 months vs. 6.8 months) for metastatic non-squamous non-small cell lung cancer (NSCLC) in the phase III IMpower150 trial ( 9 ). Evidence has also suggested that anti-PD-1 and anti-vascular endothelial growth factor (VEGF) combined therapy may be a more favorable treatment option than any single reagent for NSCLC patients who had failed on the first-line or later treatment, and this therapeutic response was not affected by VEGF mutational status ( 15 – 17 ). CheckMate 227, another phase III trial in advanced NSCLC, suggested that Nivolumab plus Ipilimumab resulted in a longer OS independent of the PD-L1 expression level ( 18 ).…”

PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake

“…Despite some disadvantages, checkpoint inhibitors possess a great prospect. The recent findings suggest that PD-1/PD-L1 inhibitors may be combined with other immunotherapies or traditional treatments to enhance efficacy relative to that using PD-1/PD-L1 therapy alone, which always exhibit higher response rates, reducing adverse reaction and drug resistance (Li J. et al, 2019;Zhang et al, 2019;Li et al, 2020;Shao et al, 2020;Sonpavde et al, 2020;Wan et al, 2020;Weiss et al, 2020;Zhang et al, 2020). Some researchers have shown the prospects of anti-PD-L1 and anti-CTLA-4 combination therapy, which revealed PD-L1:CD80 (CTLA-4 ligand) cis-heterodimerization inhibited both PD-L1: PD-1 and CD80:CTLA-4 interactions.…”