Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings

Our plain-English summary of Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings, by N. Ueno, S. Banno, Y. Endo, et al (Japanese Journal of Clinical Oncology, 2019).

The study

• Authors: N. Ueno, S. Banno, Y. Endo, M. Tamura, K. Sugaya, S. Hashigaki, E. Ohki, A. Yoshimura, A. Gemma
• Journal: Japanese Journal of Clinical Oncology
• Published: 2019;49(7):676-686
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Post-marketing surveillance (PMS) was performed in Japan to obtain information on the safety and efficacy of crizotinib.

Methods: Target patients included almost all patients with anaplastic lymphoma kinase-positive non-small cell lung cancer who were administered crizotinib. The observation period was 52 weeks. In the present study, we focused on the treatment status and safety of crizotinib therapy and analyzed the real-world data obtained by this PMS (ClinicalTrials.gov: NCT01597258).

Results: The safety analysis set included 2028 Japanese patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of adverse drug reactions (ADRs) was 91.6%, and common ADRs (incidence ≥15%) were nausea (32.2%), diarrhea (24.3%), photopsia (18.9%), vomiting (17.5%) and dysgeusia (16.8%). Many patients (623 patients) discontinued treatment of crizotinib because of adverse events within 12 weeks after therapy initiation, which tended to frequently occur in the following cases: (1) elderly, (2) body weight <40 kg, (3) body surface area <1.2 m2 (4) ECOG PS 2-4, (5) higher Brinkman index and (6) history of occupational/environmental exposure such as asbestos/pneumoconiosis. The proportions of patients remaining on crizotinib therapy were 68.2% for 3 months, 55.2% for 6 months and 36.1% for 12 months, with a median duration of 7.9 months. Multivariate analysis with a Cox proportional hazard model identified 10 statistically significant patient background factors influencing the duration of crizotinib therapy.

Conclusions: No new safety concerns were observed in this PMS study. Our results provide useful information regarding the status of crizotinib therapy in the clinical setting.

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

In plain English

This post-marketing surveillance study in Japan followed almost all ALK fusion gene-positive non-small cell lung cancer patients given crizotinib between May 2012 and December 2014. The observation period was 52 weeks, and 2028 patients were included in the safety analysis. Most started at 500 mg/day. Adverse drug reactions were reported in 1858 patients (91.6%), most often nausea (32.2%). Serious reactions occurred in 518 patients (25.5%), most commonly interstitial lung disease (4.1%). There were 76 deaths for which a link to crizotinib could not be ruled out. The median time on the drug was 7.9 months (95% CI 7.03 to 8.41). Stopping within 12 weeks because of adverse events tended to happen more often in several patient groups. One of these was patients with a history of occupational or environmental exposure such as asbestos or pneumoconiosis. The main text gives no figures for that group. Asbestos exposure was not among the ten factors a statistical model linked to treatment duration. The authors concluded that no new safety concerns were observed. They noted that the study had no untreated comparison group.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Post-marketing surveillance (all-case, single-arm observational investigation) with a 52-week observation period
• Who was studied: 2028 Japanese patients with ALK fusion gene-positive non-small cell lung cancer treated with crizotinib in Japan between May 2012 and December 2014 (safety analysis set)
• Exposure: The drug crizotinib, started at 500 mg/day in 94.2% of patients. Asbestos appears only as one patient background factor (a history of occupational or environmental exposure such as asbestos/pneumoconiosis). It is not the subject of the study.
• Main results:
  • Adverse drug reactions were reported in 1858 of 2028 patients (91.6%), with 7798 reports in total.
  • The most common adverse drug reaction was nausea, in 32.2% of patients. The others listed were diarrhea (24.3%), photopsia (18.9%), vomiting (17.5%) and dysgeusia (16.8%).
  • Serious adverse drug reactions occurred in 518 patients (25.5%), with 842 reports in total.
  • The most common serious adverse drug reaction was interstitial lung disease, in 4.1% of patients.
  • There were 76 deaths for which a causal relationship with crizotinib could not be ruled out.
  • The proportion of patients still on crizotinib was 55.2% (95% CI 53.0 to 57.3) at 6 months and 36.1% (95% CI 34.0 to 38.2) at 12 months. The figure at 3 months was 68.2%.
  • The median duration of crizotinib therapy was 7.9 months (95% CI 7.03 to 8.41).
  • The crizotinib dose was reduced in 38.4% of patients.
  • Among patients who discontinued within 12 weeks because of an adverse event, early discontinuation tended to occur more frequently in six groups: elderly patients, those with body weight under 40 kg, those with body surface area under 1.2 m2, those with ECOG PS 2 to 4, those with a higher Brinkman index, and those with a history of occupational/environmental exposure such as asbestos/pneumoconiosis. The main text gives no numbers for these groups.
  • Multivariate Cox analysis identified 10 statistically significant factors influencing the duration of crizotinib therapy: ECOG PS, age, body surface area, Brinkman index, interstitial lung disease, sex, disease duration, liver metastasis, pleural effusion and cardiovascular disease. Asbestos exposure was not among them.
• The authors' conclusion: The authors concluded that no new safety concerns were observed in this surveillance of 2028 Japanese patients treated with crizotinib in the real-world clinical setting.
• Limitations the authors state:
  • The study was single-arm, with no control group of patients not treated with crizotinib.
  • The study was conducted under Japanese-specific medical conditions, so the results may not be the same in other countries.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Non-Small Cell Lung Cancer, Environmental Exposure, Pneumoconiosis, Multivariate Analysis.

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