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Published on: February 12, 2017
Restricted mean survival time in advanced non-small cell lung cancer treated with immune checkpoint inhibitors
L Di Spazio1, L Cancanelli, M Rivano
1Hospital Pharmacy Department, S. Chiara Hospital, Trento, Italy. andrea.messori.it@gmail.com.
Objective:
The purpose of this study was to review the effectiveness of immune checkpoint inhibitors (ICIs) in the first-line treatment of advanced non-small cell lung carcinoma with wild-type epidermal grow factor receptor (EGFR) or anaplastic lymphoma kinase.
Materials And Methods:
After a standard literature search, we identified all randomized studies published on this issue. Our first inclusion criterion was the use of pembrolizumab, nivolumab, atezolizumab or durvalumab in the treatment arm versus chemotherapy in the control arm. The second criterion was the availability of information on overall survival at 2 years. The restricted mean survival time (RMST) was used to analyze the survival curves and rank the treatments.
Results:
From the eligible studies, we selected 5 randomized trials that met our inclusion criteria. These trials studied a total of 11 cohorts of patients in whom the treatment arm received ICI as monotherapy (n=3) or in combination with either chemotherapy (n=2) or other monoclonal antibodies (n=1). All the control groups (n=5) received chemotherapy. Pembrolizumab (alone or in combination) showed improvement in overall survival compared with controls, but with borderline statistical significance. Nivolumab, atezolizumab and durvalumab failed to demonstrate any survival advantage. Overall, the RMSTs provided more conservative results than those previously reported using the hazard ratio. In comparing the values of RMST across treatments, pembrolizumab combined with chemotherapy ranked first.
Conclusions:
Our results summarized the efficacy of these treatments and showed that only pembrolizumab can have a role as the first-line treatment of NSCLC. These findings are at variance with those previously reported using the hazard ratio as the outcome measure.
Insights
Immune checkpoint inhibitors (ICIs) show limited effectiveness in first-line advanced non-small cell lung cancer (NSCLC). Pembrolizumab demonstrated a survival benefit, unlike other ICIs, suggesting its potential role in NSCLC treatment.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment has evolved with immunotherapy.
- Immune checkpoint inhibitors (ICIs) are a key therapeutic class.
- First-line treatment efficacy for specific NSCLC subtypes remains an area of active research.
Purpose of the Study:
- To review the effectiveness of immune checkpoint inhibitors (ICIs) in the first-line treatment of advanced non-small cell lung carcinoma (NSCLC).
- To compare survival outcomes of different ICIs against chemotherapy in wild-type EGFR or ALK NSCLC.
- To analyze treatment efficacy using restricted mean survival time (RMST).
Main Methods:
- Systematic literature search for randomized controlled trials.
- Inclusion criteria: ICI (pembrolizumab, nivolumab, atezolizumab, durvalumab) vs. chemotherapy, with 2-year overall survival data.
- Restricted Mean Survival Time (RMST) analysis for survival curve comparison.
Main Results:
- Five randomized trials with 11 patient cohorts were analyzed.
- Pembrolizumab (alone or combined with chemotherapy) showed a statistically borderline improvement in overall survival.
- Nivolumab, atezolizumab, and durvalumab did not demonstrate a significant survival advantage over chemotherapy.
- RMST analysis yielded more conservative survival estimates compared to hazard ratios.
Conclusions:
- Pembrolizumab shows potential as a first-line treatment for advanced NSCLC, particularly in combination with chemotherapy.
- Other evaluated ICIs (nivolumab, atezolizumab, durvalumab) did not prove effective in this setting.
- RMST analysis provides a valuable alternative outcome measure for comparing survival benefits in clinical trials.
