Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study

ABSTRACT

Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy.

Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated.

Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012).

Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.

KEYWORDS:

• Family history of cancer
• multiple neoplasms
• DDR genes
• immune checkpoint inhibitors
• immunotherapy
• PD-1

Acknowledgments

This work was supported by the Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO).

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Ethics approval and consent to participate

All patients provided written informed consent to treatment with immunotherapy. All patients alive at the time of data collection provided an informed consent for the present retrospective analysis. The procedures followed were in accordance with the precepts of Good Clinical Practice and the declaration of Helsinki. The study was approved by the respective local ethical committees on human experimentation of each institution, after previous approval by the coordinating center (University of L’Aquila, Internal Review Board protocol number 32865, approved on July 24, 2018).

Authors contributions

All authors contributed to the publication according to the ICMJE guidelines for the authorship as follows:

Study conception and design: AC, PAA, CF, SB, MT, MB.

Acquisition of data: AC, RG, FP, PDM, NT, MDT, AG, KC, AT, FZ, EV, FM, MR, CA, TZ, MF, PM, AB, GCAC, FDG, MGV, FR, RRS, AP, SR, MT, MRM, AG, MAO, FM, AI, SG, SB, CZ, CM, AP, GP, DM, MCF.

Analysis and interpretation of data: AC, SB MB, PAA, CF.

Drafting of manuscript: PAA, CF, SB, MB, RB, DS.

Critical revision: PAA, CF, MT, RB, DS, MCF.

All authors read and approved the submitted version of the manuscript (and any substantially modified version that involves the author’s contribution to the study). Each author has agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

Availability of data and materials

The datasets used during the present study are available from the corresponding author upon reasonable request.

Conflicts of interest

Dr Alessio Cortellini received grants as speaker by MSD, Astra-Zeneca and Boehringer Ingelheim, grant consultancies by BMS, Roche, Novartis, Istituto Gentili, and Ipsen; Dr Marcello Tiseo received grant as speaker and advisory role by Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Pierre Fabre; Dr Maria Giuseppa Vitale received travel grants and speaker fees by BMS, Ipsen Astellas, Janssen, Novartis, and Pfizer; Dr Sebastiano Buti received grants as speaker and advisory role by BMS, Pfizer, MSD, Ipsen, Novartis, Astra-Zeneca, and research funding from Novartis; Dr. Melissa Bersanelli received honoraria as speaker at scientific events and as consultant for advisory role by BMS, Novartis, and Pfizer and research funding by Seqirus; Dr Paolo A. Ascierto has/had a consultant/advisory role for Bristol Myers-Squibb, Roche-Genentech, Merck Sharp & Dohme, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, Medimmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, he also received research funds from Bristol Myers-Squibb, Roche-Genentech, Array, and travel support from MSD.

Additional information

Funding

No funding was received.