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Checkpoint Inhibitor Meta-Analysis Sheds Light On NSCLC OS Benefit Biomarkers

Meta-analysis confirms overall survival gain with second-line checkpoint inhibitor therapy over docetaxel for advanced non-small-cell lung cancer but suggests benefit is not universal
02 Jan 2018
Immunotherapy;  Non-Small Cell Lung Cancer;  Therapy
Lynda Williams, Senior medwireNews Reporter

medwireNews: Meta-analysis of five randomised controlled trials shows that second-line use of checkpoint inhibitor therapy in patients with non-small-cell lung cancer (NSCLC) significantly extends overall survival (OS) compared with docetaxel chemotherapy.

However, further analysis demonstrated a significant relationship between OS benefit with checkpoint inhibitor use and epidermal growth factor receptor (EGFR) mutation status, the team reports in JAMA Oncology.

“With differences in OS benefits for various subgroups, this meta-analysis will be important for economic analyses where the costs required to achieve these benefits will vary”, comment Chee Khoon Lee, from the University of Sydney in New South Wales, Australia, and co-authors.

Of the 3025 participants from the CheckMate 017, CheckMate 057, KEYNOTE-010, OAK and POPLAR trials with advanced or metastatic NSCLC included in the meta-analysis, 14.1% were treated with nivolumab, 22.8% with pembrolizumab and 18.8% with atezolizumab, while 44.2% received docetaxel.

Receipt of a checkpoint inhibitor was associated with a significant 31% reduction (hazard ratio [HR]=0.69) in the overall risk of death compared with docetaxel and this outcome did not show significant heterogeneity across the trials, report the researchers.

But subgroup analysis indicated that checkpoint inhibitor use was associated with significantly longer OS than docetaxel only for patients whose tumours were wild-type for EGFR (HR=0.67).

“For patients with EGFR mutant NSCLC, our findings suggest immunotherapy should be considered only after exhaustion of other effective therapeutic options, such as EGFR tyrosine kinase inhibitors and chemotherapy”, the investigators therefore recommend.

There was also a trend towards greater OS benefit with checkpoint inhibitor use than docetaxel for patients with a KRAS mutation (HR=0.65) compared with participants with wild-type KRAS status (HR=0.86). But this difference did not reach statistical significance and the team notes that KRAS results were available for just 17% of patients.

Acknowledging that KRAS-mutated NSCLC is a “heterogeneous disease”, the researchers write that this meta-analysis therefore “does not provide sufficient evidence to recommend KRAS as a predictive biomarker for the selection of patients for checkpoint inhibitor therapy”.

Nevertheless, the benefit of checkpoint inhibitors over docetaxel was comparable for men and women (HR=0.69 vs 0.70), patients aged less than 65 years and older individuals (HR=0.71 vs 0.69), and smokers and never smokers (HR=0.69 vs 0.79). Similarly, checkpoint inhibitor receipt benefited patients with a performance statuses of 0 or 1 (HR=0.69 vs 0.68), and those with squamous and nonsquamous tumour histology (HR=0.67 vs 0.70).

The researchers also highlight that the presence or absence of central nervous system metastases did not alter OS benefit associated with checkpoint inhibitor use versus docetaxel (HR=0.76 vs 0.71).

"Although these results are generalizable only to patients with good [performance status] and who met the trial eligibility criteria, they are nevertheless encouraging", write Chee Khoon Lee et al.


Lee CK, Man J, Lord S, et al. Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma. A systematic review and meta-analysis. JAMA Oncol; Advance online publication 21 December 2017. doi:10.1001/jamaoncol.2017.4427

Last update: 02 Jan 2018

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group

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