The aim of our study was to determine the effect of homologous recombination deficiency (HRD) on prognosis and efficacy of platinum-based chemotherapy in patients with pancreatic cancer (PC). We performed PubMed and Embase database queries. We included 4 studies into the meta-analysis and 16 studies in the systematic review. Our systematic analysis showed that the average weighted median overall survival (OS) in patients with HRD with advanced PC was 19.8 and 15.6 months in patients without HRD. With platinum-based chemotherapy, the average weighted median OS in patients with HRD was 23.8 and 17.1 months in patients without HRD. Without platinum-based chemotherapy, the average weighted median OS in patients with HRD was 8.3 and 12.0 months in patients without HRD. For resected PC, our meta-analysis demonstrated that HRD status did not affect the prognosis (HR 1.03, 95% CI 0.46 to 2.33), but results were rather heterogeneous (I2=83%, p=0.003). Our systematic analysis showed that the average weighted median OS in patients with HRD was 34.6 and 27.0 months in patients without HRD. With platinum-based chemotherapy, the average weighted median OS in patients with HRD was 46.1 and 36.3 months in patients without HRD. Without platinum-based chemotherapy, the average weighted median OS in patients with HRD was 24.2 and 42.9 months in patients without HRD. Results of our meta-analysis and systematic review support the idea of platinum use in patients with HRD both in resected and metastatic PCs, although a randomised trial is warranted to make a more reliable conclusion.PROSPERO registration numberCRD42019121914.

No abstract

e16055 Background: The addition of anti-PD-1 antibodies to first-line CT is the new standard of care for pts with advanced EC. However, available data on the efficacy of such therapy in different clinical subgroups is still lacking. Therefore, we performed a meta-analysis to determine the efficacy of combination anti-PD1 and systemic CT in terms of overall survival (OS) in pts with advanced EC. Methods: We searched PubMed, proceedings of ASCO, and ESMO conferences up to February 2022. We included prospective randomized phase III trials comparing the combination of anti-PD1 and CT with CT alone as the first-line treatment option for pts with advanced EC. The primary outcome was OS. Meta-analysis was conducted by Review Manager (Ver. 5.3) software. Results: Five trials with a total of 3163 pts were included, of which 1576 received anti-PD1+CT and 1587 received CT alone. There was a significant improvement in PFS (HR, 0.62; 95% CI, 0.56-0.67; p < 0.00001; I2 = 45%, p for heterogeneity 0.12), OS (HR, 0.69; 95% CI, 0.63-0.76; p < 0.00001; I2 = 0%) and ORR (OR, 2.07; 95% CI, 1.76-2.43; p < 0.00001; I2 = 21%) in pts received anti-PD1+CT. OS was improved in pts regardless of age, race, CT regimen, presence of liver metastases, ECOG PS, or histology. Subgroup analysis suggested that the addition of anti-PD1 have a better effect in pts with PDL expression on tumor cells > 1, ≥ 10, and < 10 and in pts with CPS ≥ 10, but not in pts with PDL < 1. We found a tendency towards survival advantage in pts with CPS < 10. No survival benefit was observed in women (tab). Conclusions: Improved OS was found to be associated with addition of anti-PD1 antibodies to systemic CT in different patient subgroups with advanced EC, except for female and in pts with low PDL expression. Despite of meta-analysis results we need prospective randomized trial for pts with CPS < 10.[Table: see text]

posters P À 049 A population study of correlation between the treatment rate for monoclonal antibodies (Mabs) and mortality rate in patients with metastatic colorectal cancer (mCRC) in Russia

Pts received 1500 mg/m 2 NUC-3373 +/-400 mg/m 2 LV on Days 1 and 15 of a 28-day cycle. Plasma and PBMC samples were collected during first 2 cycles. Safety was assessed throughout.Results: PK profiles from 17 matched pairs from Q2W dosed pts were available (n ¼ 21 pts). PK parameters for NUC-3373 were similar +/-LV and interpatient variability was low. Increasing intracellular FUDR-MP concentrations were associated with an increase in intracellular dUMP concentrations. NUC-3373 was well tolerated +/-LV. Highest grade treatment-related adverse events (TRAEs) were grade 3 hyponatremia (1 pt) and grade 4 bilirubin increased (1 pt). No pts discontinued NUC-3373 due to TRAEs.Conclusions: NUC-3373 demonstrated a favourable PK profile with a long plasma halflife and high volume of distribution. The association between increasing FUDR-MP with increasing dUMP concentrations indicates NUC-3373's ability to inhibit TS, preventing conversion of dUMP to dTMP. PK parameters for NUC-3373 +/-LV were similar indicating LV has no PK interaction with NUC-3373. NUC-3373 was well tolerated +/-LV. These findings suggest that LV is an appropriate combination partner for NUC-3373. Clinical trial identification: NCT03428958.Legal entity responsible for the study: NuCana plc.