In the immuno-oncology era, is anti-PD-1 or anti-PD-L1 immunotherapy modifying the sensitivity to conventional cancer therapies?

Introduction The advent of anti-programmed death receptor-1/ligand-1 antibodies (anti-PD(L)1) is profoundly changing the therapeutic strategy of oncology. As anti-PD(L)1 modulate tumour microenvironment, it might impact sensitivity to conventional cancer therapy (CCT). Therefore, we explored whether sensitivity to CCT was different before and after anti-PD(L)1 therapy. Methods Patients who started anti-PD(L)1 treatment at Gustave Roussy Cancer Centre between February 2012 and December 2015, and who received at least one line of CCT immediately before and immediately after anti-PD(L)1, were eligible. We analysed progression-free survival (PFS) and overall response rate (ORR) of the CCT line immediately before (PFSpre/ORRpre) and after (PFSpost/ORRpost) anti-PD(L)1. PFS and ORR were compared using Wilcoxon signed rank and McNemar tests in a paired data subset for patients having received identical class of CCT pre and post anti-PD(L)1 therapy. Results Among 118 eligible patients, 65% received anti-PD1 and 35% anti-PD-L1 agents. Median PFSpre versus PFSpost was 4.7 versus 3.5 months (p = 0.011), respectively; it was 5.7 versus 6.8 months (NS) for patients who derived clinical benefit from immunotherapy and 3.9 versus 3.0 months (p = 0.012) for patients who were primary resistant to anti-PD(L)1 therapy. Subgroup analysis did not reveal any significant difference in PFS or ORR before versus after anti-PD(L)1 therapy according to CCT class or to its ability to induce immunogenic cell death. Conclusion Patients who derive benefit from immune therapies tend to have better PFS on conventional therapies after having received the anti-PD(L)1 agent. Further studies on larger data sets are warranted to confirm these findings.