83P - Association of immune-related adverse events and the efficacy of anti-PD-(L)1 monotherapy in patients with advanced NSCLC: a cohort study adjusting for immortal-time bias

Background

The association between immune-related adverse events (irAEs) and survival outcomes in non-small cell lung cancer (NSCLC) patients treated with programmed-death-(ligand)1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).

Methods

We retrospectively enrolled 425 patients with advanced NSCLC who received anti-PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAEs (n=127) and non-irAEs (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark and time-dependent Cox analyses were performed in addition to conventional analysis to eliminate ITB.

Results

127 patients (29.9%) experienced 186 irAEs, with 89 single-organ and 38 multi-organ. 42 skin irAEs, 39 thyroid irAEs, 27 pneumonitis, 25 hepatic irAEs, and some less frequent irAEs et.al. With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs 3.4 months, P<0.0001) and OS (31.4 vs 14.0 months, P<0.0001), and this positive association persisted in landmark (3-, 6-, and 9-month; all P<0.05) and time-dependent Cox analyses (adjusted HR for PFS=0.55, 95% CI 0.43-0.71; for OS=0.53, 95% CI 0.41-0.70). For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.

Conclusions

After adequately adjusting ITB, the occurrence of overall irAEs predicts for favourable efficacy of anti-PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.