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

Abstract

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.

Keywords: Anti-PD1; Anti-PDL1; Immunotherapy; Response to conventional cancer treatment.