Treatment discontinuation and re-initiation of anti-PD-(L)1 agents in metastatic cancers.

Introduction: Immune checkpoint inhibitors (ICIs) are approved in multiple indications for cancer care. Most of the clinical trials have not questioned shorter than until disease progression approaches. In this study, we present results from a cohort of multiple advanced cancers treated with restricted anti-PD-(L)1 therapy.

Methods: All patients with advanced cancers treated with anti-PD-(L)1 therapy outside clinical trials at Oulu University Hospital 2014-19 were retrospectively identified from pharmacy records. Clinical variables, treatment history and survival were collected.

Results: 106 patients with median age of 66 years with lung cancer (n = 45, 42.5%), melanoma (n = 30, 28.3%), renal and bladder cancers (GU cancers) (n = 26, 24.5%), head and neck (H&N) cancer (n = 4, 3.8%), and colorectal cancer (n = 1, 0.9%) were included in the study. The median (m) OS for the whole population was 14 months (CI 9.7-18.3), 9 months (CI 6.3-11.7) for patients with no IO-free period (n = 64, 62.1%), and 27.0 months (CI 20.6-33.4, p = 0.000001) for patients (n = 39) with IO-free period. The mIO-free survival was 10.0 months (CI 7.1-12.9) for the whole cohort, 8.0 months (CI 1.7-14.3) for lung cancer, 23.0 months (CI 2.6-43.4) for melanoma, and 14.0 months (CI 0.0-20.4) for GU cancer. From the IO-free cohort, 19 patients needed re-treatment during follow-up, of which 8 were re-challenged with anti-PD-(L)1 therapy. The clinical benefit rate of anti-PD-(L)1 re-challenge was 37.5%.

Conclusions: Our study shows that long IO-free periods can be achieved with limited duration of anti-PD-(L)1 therapy with excellent survival outcomes, and that anti-PD-(L)1 re-challenge is feasible in clinical practice.