Clinical factors associated with early progression and grade 3–4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab
April
Clinical factors associated with early progression and grade 3±4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab
Coraline Dumenil 0 1
Marie-Ange Massiani 1
Jennifer Dumoulin 0 1
Violaine Giraud 0 1
Sylvie Labrune 0 1
Thierry Chinet 0 1
Etienne Giroux Leprieur 0 1
0 Department of Respiratory Diseases and Thoracic Oncology, APHPÐAmbroise Pare Hospital , Boulogne- Billancourt , France , 2 Department of Medical Oncology, Ren e Huguenin Hospital, Curie Institute , Saint- Cloud, France, 3 EA4340 , University of Versailles Saint-Quentin-en-Yvelines, Paris-Saclay University , Boulogne-Billancourt , France
1 Editor: Ramon Andrade De Mello, Universidade do Algarve Departamento de Ciencias Biomedicas e Medicina , PORTUGAL
The prognosis of advanced non-small-cell lung cancer (NSCLC) has been improved by development of immune checkpoint inhibitors (ICIs) such as nivolumab for second-line treatment. As phase III trials include only selected patients, we here investigated the clinical factors associated with efficacy and safety of nivolumab in `real life' patients with advanced NSCLC.
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Data Availability Statement: All relevant data are
within the paper and its Supporting Information
file.
Funding: The authors received no specific funding
for this work.
Competing interests: I have read the journal's
policy and the authors of this manuscript have the
following competing interests: MAM: advisory
board for Bristol-Myers-Squibb; EGL: research
Methods
Results
Clinical and histological characteristics, therapies and survival data of all consecutive
patients with advanced NSCLC included prospectively and treated by nivolumab in two
French academic hospitals between February 2015 and December 2016 were examined.
Sixty-seven patients were included, mostly male (69%), current or former smokers (87%)
with PS <2 (73%). Median age was 68.5 years and 42% were aged 70 years. According to
uni- and multi-variate analyses, only PS 2 (OR = 0.17, 95% CI 0.03±0.99, p = 0.049) and
number of previous treatment lines (OR = 0.33, 95% CI 0.13±0.85, p = 0.022) were
significantly negatively associated with tumor control. Worse progression-free survival (PFS) was
significantly associated with PS 2 (HR = 5.17, 95% CI 1.99±13.43, p = 0.001) and use of
steroids (HR = 3.27, 95% CI 1.39±7.69, p = 0.006). Worse overall survival was associated with
symptomatic brain metastasis (HR = 3.15, 95% CI 1.23±8.85, p = 0.029). Treatment-related
adverse events occurred in 47 patients (70%), symptomatic brain metastasis being
significantly associated with Grade 3 toxicity (OR = 8.13, 95% CI 1.21±55.56, p = 0.031). Age
and nutritional status were not associated with response, PFS, OS or toxicity.
grants from Bristol-Myers-Squibb. This does not
alter our adherence to PLOS ONE policies on
sharing data and materials. The other authors did
not have competing interests.
Conclusion
Our results suggest that nivolumab is not beneficial or safe for patients with PS 2 and
symptomatic brain metastases.
Introduction
Non-small cell lung cancer (NSCLC) is the leading cause of cancer related±death worldwide
[1]. The treatment of NSCLC has recently been improved by development of immune
checkpoint inhibitors (ICIs), which target inhibitor pathways such as programmed death 1 (PD1)/
programmed death-ligands 1 (PDL1), thus blocking the immune responses of
tumor-infiltrating lymphocytes, allowing proliferation of tumor cells [2]. Nivolumab, a fully human IgG4
PD-1 ICI antibody, was the first agent to show efficacy in second-line treatment of patients
with NSCLC in two recent phase III trials and had a favorable safety profile compared with
docetaxel [3, 4]. A new era of immunotherapy has begun with encouraging results from
randomized phase II and III trials, putting into question and extending the potential indications
for ICIs for NSCLC [5]. However, patients included in these trials all had performance status
(PS) 0±1, did not have active or untreated brain metastases, and were relatively young (only
7% and 11% of 75 years-old patients in Checkmate-057 and Checkmate-017 trials,
respectively). Thus, benefit and safety of ICIs for all patients with advanced NSCLC in `real life' is
still unanswered. Seventeen percent of patients with Stage IV NSCLC have central nervous
system (CNS) metastases at initiation of first-line treatment [6] and around one third of patients
with NSCLC have a PS of 2 [7].
The objectives of this study were to determine the clinical factors associated with the
efficacy and safety of nivolumab in `real-life' patients with advanced NSCLC, including elderly
patients and those with poor PS, brain metastases, or poor nutritional status at the time of
nivolumab.
Materials and methods
Patients
Records of all consecutive patients with advanced NSCLC treated by nivolumab (3 mg/ kg
every two weeks) between February 2015 and December 2016 were retrieved from a database
of prospectively collected information on all p (...truncated)