Family History of Cancer as Surrogate Predictor for Immunotherapy with Anti-Pd1/Pd-L1 Agents: Preliminary Report of the Fami-L1 Study

Abstract

Aim: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. Materials & methods : We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. Results: In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p = 0.0024), disease control rate (p = 0.0161), median time to treatment failure (p = 0.0203) and median overall survival (p = 0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p = 0.0268 and p = 0.0272, respectively). Conclusion: This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy.

Family history of cancer and DNA damage response genes: Two sides of the same coin?

“…In the preliminary analysis of the FAMI‐L1 study, 211 advanced cancer patients (NSCLC, melanoma, and renal cell carcinoma) treated with anti‐PD‐1/PD‐L1 agents were evaluated. We found that FHC was significantly related to better objective response rate, disease control rate, longer time to treatment failure, and overall survival . Analogous findings were observed for a diagnosis of multiple neoplasms; however, the results did not reach statistical significance .…”

“…We found that FHC was significantly related to better objective response rate, disease control rate, longer time to treatment failure, and overall survival . Analogous findings were observed for a diagnosis of multiple neoplasms; however, the results did not reach statistical significance . Clearly, our results are not conclusive; the aim of the preliminary analysis was only to test the hypothesis, describing from afar something that we are still not able to explain up close.…”

“…4 Analogous findings were observed for a diagnosis of multiple neoplasms; however, the results did not reach statistical significance. 4 Clearly, our results are not conclusive; the aim of the preliminary analysis was only to test the hypothesis, describing from afar something that we are still not able to explain up close.…”

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

“…And the predictive value of pathological feature needs to be verified in large sample size. Intriguingly, a recent pilot study revealed the correlation between family history of cancer and treatment effect of anti-PD-1/PD-L1 therapy [ 114 ]. Multiple cancers patients with family history of cancer had significantly improved objective response rate ( p = 0.0024) and favorable outcome [ 114 ].…”

Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review

“…ICB can also be effective in hereditary tumors associated with other mechanisms of DDR, generating a high number of somatic mutations (consequently a high TMB). A recent study revealed that a positive family history of cancer was significantly associated with a better objective response rate (ORR), disease control rate (DCR), median time to treatment failure (TTF) and median OS in patients treated with ICB, raising the question whether this effect on hereditary tumors could also be seen in breast cancers (BC) associated with a defective DNA damage response [15]. In particular, the hereditary breast and ovarian cancer syndrome is associated with the presence of germline mutations in BRCA1 or BRCA2 genes [16].…”