DNA damage repair mutations in pancreatic cancer- prognostic or predictive?

Objective: The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain.Methods: After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh.Results: Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I-2 = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I-2 = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I-2 = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I-2 = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I-2 = 65%) and for those after non-PtCh (HR=0.87; I-2 = 0%), the presence of DDRm did not show a significant association with longer OS.Conclusion: 1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials.

Automated summary

The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) remains uncertain. This study analyzed multiple studies and found that DDRm was associated with a longer overall survival (OS) in advanced-stage PC patients, regardless of PtCh exposure. The first-line PtCh (1L-PtCh) also improved progression-free survival (PFS) in advanced-stage PC with DDRm. However, for resected PC patients, the presence of DDRm did not significantly impact OS, whether they received PtCh or not. Further prospective trials are needed to verify the prognostic value of DDRm.