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 FHCnegative 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.

Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice

“…This is of particular importance to determine whether the influence on clinical outcomes might be driven by associative rather than causative links, especially given the high prevalence of polypharmacy in patients with cancer. 14 Recently, we created a large multicenter, observational study of patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical practice, already subject of several analyzes, [15][16][17][18][19][20] and we now gathered the baseline concomitant medication information for the same population, in order to evaluate their impact on clinical outcomes.…”

Clinical factors associated with outcome in solid tumor patients treated with immune-checkpoint inhibitors: a single institution retrospective analysis

“…In the multicenter retrospective study of 211 advanced cancer patients, Cortellini and colleagues also found statistically significant correlation between family history of cancer and ICI response with improved ORR (p = 0.0024), DCR (p = 0.0161), median time to treatment failure (p = 0.0203), and median OS (p-0.0221) [ 28 ]. Expanded analyses of 811 advanced cancer patients upheld family history of cancer as an independent predictor of PFS and OS in multivariable analyses [ 29 ]. Our data supports their assessment that family history of cancer may be a surrogate for known (and yet to be identified) syndromes of inherited cancer susceptibility.…”

Family history of cancer is associated with poorer prognosis in oral squamous cell carcinoma

“…In a multicenter retrospective study by Cortellini et al (Cortellini et al, 2018; Cortellini et al, 2020), FHC‐positive patients experienced greater benefit from immune checkpoint inhibitors, suggesting that underlying genetic alterations may lead to changes in immune sensitivity. As incorporating germline genetic testing into medical management has occurred in other tumors, for example, breast, ovarian, and bladder cancer, it may be proved helpful 1 day in OSCC treatment decisions (Nicolosi et al, 2019).…”