The safety of second-line treatment options for non-small cell lung cancer

ABSTRACT

Introduction: Non-small-cell lung cancer (NSCLC) patients after first-line therapy ultimately suffer progression. At this time, many patients still have a good performance status and can be considered for further active treatment. Two chemotherapeutic agents, docetaxel and pemetrexed (only in non-squamous histology), and the biological drug anti-epidermal growth factor receptor (EGFR) erlotinib, were approved for clinical use in the second-line treatment of NSCLC patients. In the last few years further new second-line therapies have become available in the clinical practice.

Areas covered: This review will discuss the adverse events of the pivotal trials ledding to the approval of second-line therapies for the treatment of not oncogene-addicted NSCLC patients.

Expert opinion: In recent years, new second-line options for NSCLC are: the anti-EGFR, afatinib (only in squamous NSCLC); the anti-angiogenics, nintedanib (only in lung adenocarcinoma) and ramucirumab, in combination with docetaxel; the immunotherapeutics, nivolumab, pembrolizumab, and atezolizumab. In the second-line approach, the main endpoint of treatment should always be survival, but with great respect for symptoms palliation and preserving patients’ quality of life. Therefore, differing toxicity profiles of the available therapeutic options are often a deciding factor in second-line setting for NSCLC.

KEYWORDS:

• Afatinib
• anti-angiogenic
• atezolizumab
• immunotherapy
• nintedanib
• nivolumab
• NSCLC
• pembrolizumab
• ramucirumab
• second-line

Article highlights

• Almost all non-small-cell lung cancer (NSCLC) patients after first-line therapy ultimately suffer progression. At the time of disease progression, many patients still have a good performance status and can be considered for further active treatment.

• Two chemotherapeutic agents, docetaxel and pemetrexed (only in non-squamous histology), and the biological drug anti-epidermal growth factor receptor (EGFR) erlotinib, were approved for clinical use in the second-line treatment of recurrent NSCLC patients.

• In the last years several new drugs granted the approval for second-line therapy of NSCLC patients: the anti-EGFR afatinib, anti-vascular growth factor receptor (VEGFR) nintedanib, and ramucirumab, and immunotherapeutics nivolumab, pembrolizumab, and atezolizumab.

• Afatinib showed a statistically, but not clinically meaningful, survival improvement than erlotinib in squamous NSCLC patients but with a worst toxicity in terms of grade ≥ 3 diarrhea, and skin rash.

• Nintedanib combined with docetaxel is registered for the treatment of lung adenocarcinoma because only in this NSCLC histology demonstrated a survival improvement with a slight increase in grade ≥ 3 toxicities than docetaxel single-agent also adding anti-angiogenic-specific adverse events which were manageable.

• Ramucirumab plus docetaxel showed statistically improvements of outcomes in any histology NSCLC versus docetaxel alone with a slight increase of grade ≥ 3 any toxicity but with similar grade ≥ 3 anti-angiogenic-specific adverse events.

• Nivolumab, pembrolizumab and atezolizumab showed a statistically and clinical survival improvement with a clear better safety profile compared to docetaxel. Any grade immunorelated adverse events were about 10% and rarely of grade ≥ 3.

• Comorbidities, patients’ risk factors, and the different drug safety profiles are often deciding factors in choosing the effective second-line therapy for NSCLC patients, to find the most appropriate therapy balancing better outcomes and lowest possible toxicity.

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Declaration of interest

A Rossi declares speaker’s bureau participation for Roche, Boehringer Ingelheim and AstraZeneca; and advisory board participation for Eli-Lilly, AstraZeneca and Roche. P Maione declares advisory board participation for Eli-Lilly and Roche. C Gridelli declares speakers bureau and advisory board participation for Roche, Boehringer Ingelheim and Eli-Lilly. 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 was not funded.