Family history of cancer as surrogate predictor for immunotherapy with anti-PD-1/PD-L1 immune checkpoint inhibitors: The FAMI-L1 study.

Abstract

2559 Background: In the preliminary analysis of the FAMI-L1 study, we found a significant association between family history of cancer (FHC) and better clinical outcomes with anti-PD1/PD-L1 inhibitors. Methods: We retrospectively evaluated advanced cancer patients treated with single agents PD1/PD-L1 inhibitors. Patients were categorized as follow: FHC-high (in case of at least one cancer diagnoses in both straight and collateral family line), FHC-low (in case of a cancer diagnoses in only one family line) and FHC-negative. FHC was collected till the second degree of relatedness. Results: Between September 2013 and May 2018, 772 consecutive patients were evaluated. Median age was 68 years; male/female ratio was 521/251. Primary tumors were: NSCLC (58.3%), melanoma (22.1%), renal cell carcinoma (16.6%) and others (3%). 114 patients (14.9%) had ECOG-PS ≥ 2. 341 patients (44.3) were FHC-positive: 268 of them (34.75) were FHC-low while 74 (9.6%) were FHC-high. FHC-high patients had a significantly higher incidence of irAEs compared to FHC-negative (55.4% vs 35.6%; p = 0.0012) and to FHC-low (41.4%; p = 0.0323). No significant differences were found in terms of ORR among subgroups (data not shown). At median follow-up of 15.8 months, median PFS was 9.1 months (95%CI: 8.1-10.4; 452 events) and median OS was 19.7 months (95%CI: 15.7-24.4; 436 censored). No significant differences were found regarding PFS (data not shown). Median OS of FHC-high patients was 31.6 months (95%CI: 26.2-31.6; 50 censored patients), which was significantly longer than 18.2 months (95%CI: 14.7-21.3; 229 censored patients) of FHC-negative patients (HR = 0.60 [95%CI: 0.39–0.92), p = 0.0213). No significant differences in terms of OS were found between FHC-high/low patients (data not shown). After adjusting for primary tumor, sex, treatment-line, number of metastatic sites and ECOG-PS, FHC-high was confirmed an independent predictor of longer OS compared to FHC-negative (HR: 0.57 [95%CI: 0.37-0.88], p = 0.0098). Conclusions: FHC-high seems to be an independent predictor for longer OS in cancer patients treated with anti-PD-1/PD-L1. DNA damage and response (DDR) genes alterations may underlie that results.