Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies

A Pooled Analysis of Phase III Trials

Elvire Pons-Tostivint, MD; Aurélien Latouche, PhD; Pauline Vaflard, MD; Francesco Ricci, MD, PhD; Delphine Loirat, MD, PhD; Ségolène Hescot, MD, PhD; Marie-Paule Sablin, MD; Roman Rouzier, MD, PhD; Maud Kamal, PhD; Claire Morel, MSc; Charlotte Lecerf, MSc; Vincent Servois, MD; Xavier Paoletti, PhD; Christophe Le Tourneau, MD, PhD

Disclosures

JCO Precis Oncol. 2019;2019(3) 

In This Article

Abstract and Introduction

Abstract

Purpose: Immune checkpoint inhibitors (ICIs) have been demonstrated to improve overall survival (OS) in several tumor types. Durable responses have been reported with these agents in patients with melanoma and lung cancer. We aimed to quantify the proportion of patients who experience durable responses on ICIs and to compare it with other drug classes.

Patients and Methods: We retrieved published phase III randomized trials that included at least one ICI arm in the recurrent and/or metastatic setting. A durable response to treatment was defined as a progression-free survival that exceeded three times the median progression-free survival of the whole population. The proportion of patients who experienced an OS that exceeded two times the median OS of the whole patient population also was estimated.

Results: Nineteen studies involving 11,640 patients treated in 42 treatment arms (26 ICI and 16 non-ICI arms) were included. The mean proportion of patients who experienced a durable response was 2.3 times higher in those treated with an ICI compared with those treated in the control arms (25% v 11%). Durable responses were more frequent in patients treated with anti–PD-1/PD-L1 agents than in patients treated with anti–CTLA-4 agents (28% v 18%). The mean proportion of patients who had an OS that exceeded two times the median OS was also higher in those treated with ICIs than in those treated in the control arms (30% v 23%). In multivariable analysis, the effects of treatment with anti–PD-1/PD-L1 agents and of first-line treatment were statistically associated with a higher mean proportion of durable responses.

Conclusion: Durable responses were more frequent in patients treated with ICIs, although they also occurred in patients treated with other drug classes.

Introduction

Immune checkpoint inhibitors (ICIs) that target cytotoxic T-lymphocyte protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand PD-L1 have been demonstrated to improve overall survival (OS) in several tumor types.[1–12] In 2011, ipilimumab, a fully human immunoglobulin G1 monoclonal antibody that targets CTLA-4, was the first ICI to be approved by the Food and Drug Administration for the treatment of patients with previously treated advanced melanoma because of a significant improvement in OS in two randomized phase III clinical trials.[8,13] Anti–PD-1 ICIs, including nivolumab and pembrolizumab, and anti–PD-L1 ICIs, including atezolizumab, avelumab, and durvalumab, were subsequently approved by the Food and Drug Administration not only in recurrent melanoma but also in several other tumor types, including non–small-cell lung cancer (NSCLC), renal cell carcinoma, head and neck squamous cell carcinoma, urothelial carcinoma, Merkel cell carcinoma, and Hodgkin lymphoma.

Patients with cancer with recurrent and/or metastatic disease usually have been considered as being incurable. Achievement of a durable response is a major goal for these patients, although cure is the ultimate aim of cancer research in this situation. Durable response has been advocated to be one of the specificities of ICIs among others.[14] Plateaus in OS Kaplan-Meier curves of approximately 20% support this observation, as exemplified in patients with melanoma treated with ipilimumab and in patients with NSCLC treated with nivolumab.[15,16] We aimed to evaluate whether durable responses were specific to ICIs by quantifying the proportion of patients who experience durable responses with ICIs and to compare it with other drug classes.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....