Methodological interpretation of subgroup analysis by histological subtype for perioperative toripalimab in...

Pivotal study on perioperative toripalimab in resectable non-small-cell lung cancer showed population differences by histological subtype compared with other immunotherapy regimens, raising doubts about therapeutic positioning. The aim of this study was to interpret the methodological analysis by subgroups according to histological subtype of perioperative toripalimab in resectable non-small-cell lung cancer.

Validated subgroup analysis applicability tool was used. This tool had two parts: preliminary questions to directly rule out analysis without relevant minimum conditions, and checklist. This checklist assessed statistical association, biological plausibility and consistency of subgroup results, and related these criteria to recommendations on applicability.

Preliminary question regarding differences in effect between subgroups p(i) < 0.1 was answered negatively, and checklist was not applied due to direct discard. Even if the checklist had been applied, statistical association criterion would have been rated 'null' due to absence of statistically significant differences. Biological plausibility would have been rated 'probable' due to non-squamous histology being a negative prognostic factor. Consistency would have been rated 'null' for absence of heterogeneity between subgroups in similar studies.

This methodological interpretation recommended against applying histology-based subgroup results for perioperative toripalimab in resectable non-small-cell lung cancer, avoiding ruling out the use of toripalimab in the non-squamous subgroup.