The role of nivolumab combined to immunotherapy and/or chemotherapy in the first-line treatment of advanced Non Small Cell Lung Cancer

ABSTRACT

Introduction: One of the latest breakthroughs in the treatment of advanced Non Small Cell Lung Cancer (NSCLC) is represented by PD-1/PD-L1-targeting Immune Checkpoint Inhibitors (ICIs). However, only a limited subset of advanced NSCLC patients can receive first-line ICI monotherapy (advanced NSCLC patients without driver mutations and with a PD-L1 expression ≥50% or ≥1%) and naïve ICI-respondent patients represent an even more limited subgroup of patients, which eventually experience progression of disease after approximately 7–11 months. Therefore, different strategies are being evaluated to obtain a higher response rate and a more durable clinical response in this setting. A very encouraging one is represented by ICI-combination therapies, i.e. the use of an ICI combined to cytotoxic chemotherapy and/or another immunotherapeutic agent.

Areas covered: This paper aims to assess currently available data from trials evaluating nivolumab-based first-line combination therapies.

Expert opinion: Nivolumab-based combinations regimens will represent one of the standard treatments for naïve advanced NSCLC patients in a near future. However, in order to fully exploit these combination therapies, additional studies assessing potential predictive and/or prognostic biomarkers are required to better clarify which patients are more likely to benefit from these regimens, alongside with studies investigating safer and more durable second-line treatments.

KEYWORDS:

• Advanced NSCLC
• combination therapies
• chemotherapy
• nivolumab
• ipilimumab
• treatment algorithms

Article highlights

• Only a limited subset of advanced NSCLC patients can receive first-line ICI monotherapy (advanced NSCLC patients without driver mutations and with a PD-L1 expression ≥50% or ≥1%) and naïve ICI-respondent patients represent an even more limited subgroup of patients, that eventually experience progression of disease after approximately 7–11 months.

• A very encouraging strategy to obtain higher response rates and a more durable responses is represented by ICI-combination therapies.

• Thanks to the data coming from the CheckMate-227 part 1a trial, the nivolumab plus ipilimumab combination has been granted FDA (US Food and Drug Administration) approval for the treatment of naïve advanced NSCLC patients without targetable driver mutations and with a PD-L1 TPS (Tumor Proportion Score) ≥1%

• Due to the data from the CheckMate 9LA study, FDA granted regulatory approval to the nivolumab plus ipilimumab plus 2 cycles of platinum-based standard-of-care chemotherapy combination for the treatment of naïve advanced NSCLC patients without targetable driver mutations.

• Nivolumab-based combinations regimens will represent one of the standard treatments for naïve advanced NSCLC patients in a near future.

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Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Declaration of interest

C Gridelli received honoraria as speaker bureau and advisory board member from Astra Zeneca, BMS, MSD and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper is not funded.