Safety profiles of first-line therapies for metastatic non-squamous non-small-cell lung cancer

ABSTRACT

Introduction: Lung cancer still represents the leading cause of death for cancer. About the 70% of diagnosis are in advanced-stage. Non-small-cell lung cancer (NSCLC) represents the 85% of all diagnosed lung cancers and non-squamous histology represents the 40% of all NSCLC. First-line therapies increase survival, control symptoms and improve quality of life, compared with best supportive care. It is crucial to choose a treatment with a low impact on patient’s life considering the related toxicities.

Areas covered: Adverse events (AEs) of first-line therapies for non-squamous NSCLC are here reviewed and discussed, from evidences in clinical trials conducting to drugs approval.

Expert opinion: For advanced disease, palliation and preserving patients QoL are still the primary goal of treatment. Therefore, differing toxicity profiles are often a deciding factor in first-line and also maintenance setting for non-squamous NSCLC.

Special attention is necessary to renal function and drugs’ nephrotoxicity. Moreover, it is to consider the specific AEs of drugs classes: hypertension, bleeding, and proteinuria, for anti-VEGF therapy; skin toxicity, diarrhea, interstitial lung disease for TKIs; vision disorders, and hepatotoxicity for ALK-inhibitor. It is important to select patients for a treatment on the basis of their comorbidities and the presence of risk factors.

KEYWORDS:

• Afatinib
• bevacizumab
• crizotinib
• erlotinib
• first-line therapy
• gefitinib
• maintenance therapy
• non-squamous non-small-cell lung cancer
• pemetrexed

Article highlights

• Pemetrexed demonstrated efficacy, especially in non-squamous NSCLC. It is globally well tolerated for an extended period too. B12 and folate supplements improve its tolerability.

• Bevacizumab is approved only for non-squamous histology because of the increased AEs, especially pulmonary hemorrhage, reported among patients with squamous NSCLC. Bevacizumab had a specific toxicity profile, characterized by hypertension, bleeding, proteinuria, thrombotic events, wound-healing complications, and gastrointestinal perforation. Generally, AEs occur in the first cycles of treatment and are well tolerated.

• Some AEs of TKIs are related to the inhibition of specific molecular target in normal tissue, resulting in acne and skin rash. Other TKIs AEs are related to their oral formulation, causing gastrointestinal symptoms. The adequate management of these AEs lead to a better patients’ compliance to therapy with a better QoL.

• ALK inhibitors could cause vision disorders, diarrhea, edema, hepatic events, ILD, and cardiotoxicity with Q-wave-T-wave interval prolongation and bradycardia. In particular, ceritinib is burdened by a higher rate of grade >3 diarrhea and nausea, while alectinib is better tolerated.

• Renal failure is often reported in lung cancer patients, because of platinum-based chemotherapy also. Monitoring renal function only with serum creatinine levels is not sufficient. It is important to reach an early diagnosis of renal injury because of anemia related to renal failure, which could worsen lung cancer-related anemia and patients’ QoL.

• Comorbidities, patients’ risk factors, and the different drug toxicities are often deciding factors in choosing an effective regimen for non-squamous NSCLC, to find the treatment leading to better response with the lowest possible toxicity.

This box summarizes key points contained in the article.

Declaration of interest

C Gridelli has received fees as speaker bureau and advisory board member for Eli Lilly, Roche, Pfizer and Novartis. 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.