The effect of best response to prior anticancer therapy on efficacy outcomes in the NAPOLI-1 trial of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy (2018)

Introduction: In the NAPOLI-1 phase 3 study of patients with mPDAC who progressed following gemcitabine-based therapy (NCT01494506), nal-IRI+5-FU/LV significantly increased median overall survival (mOS) vs 5-FU/LV control (6.1 vs 4.2 months; unstratified hazard ratio [HR] 0.67 [0.49–0.92]; P = 0.012). Best response to prior therapy may influence treatment outcomes, prognosis and subsequent therapy choices. Methods: This post-hoc analysis explored outcomes in NAPOLI-1 patients based on best response to prior anticancer therapy. Treatment response groups were: complete response/partial response as prior best response (CR/PR) vs not CR/PR, and complete response/partial response/stable disease as prior best response (CR/PR/SD) vs not CR/PR/SD. Results: Prior to study entry, 55/417 patients (13%) had CR/PR on prior anticancer therapy, and 211 (51%) had CR/PR/SD. In the overall intent-to-treat (ITT) population, trends towards improved outcomes were observed in CR/PR vs not CR/PR patients (mOS 5.6 vs 4.8 months, HR = 0.73, P = 0.08; median progression-free survival [mPFS] 3.8 vs 2.4 months, HR = 0.73, P = 0.06; objective response rate [ORR] 13% vs 6%, P = 0.085). mOS, mPFS and ORR were similar in CR/PR/SD vs not CR/PR/SD patients (mOS 4.9 vs 4.9 months, HR = 0.95, P = 0.68; mPFS 2.5 vs 2.6 months, HR = 1.00, P = 0.95; ORR 7% vs 7%, P = 1.00). In the nal-IRI+5-FU/LV arm, a trend towards improved mOS, mPFS and ORR was observed in patients with CR/PR (n = 11) vs not CR/PR (n = 106) (mOS 9.3 vs 6.1 months, HR = 0.64, P = 0.34; mPFS 4.2 vs 3.0 months, HR = 0.53, P = 0.13; ORR 27% vs 15%). mOS, mPFS and ORR were similar in patients with CR/PR/SD (n = 58) vs not CR/PR/SD (n = 59) (mOS 6.2 vs 6.1 months, HR = 1.04, P = 0.88; mPFS 4.0 vs 3.3 months, HR = 1.18, P = 0.45; ORR 14% vs 19%, P = 0.62). Patients with CR/PR numerically benefited from treatment with nal IRI+5 FU/LV (n = 11) vs 5 FU/LV (n = 21) (mOS 9.3 vs 5.1 months, HR = 0.46, P = 0.14; mPFS 4.2 vs 1.4 months, HR = 0.33, P = 0.03; ORR 27% vs 0, P = 0.03). Patients with not CR/PR also benefited from treatment with nal IRI+5-FU/LV (n = 106) vs 5-FU/LV (n = 98) (mOS 6.1 vs 4.0 months, HR = 0.69, P = 0.03; mPFS 3.0 vs 1.5 months, HR = 0.58, P < 0.01; ORR 15% vs 1%, P < 0.01). Similar trends towards improved outcomes were also observed in patients with CR/PR/SD when treated with nal-IRI+5-FU/LV (n = 58) vs 5-FU/LV (n = 61) (mOS 6.2 vs 4.8 months, HR = 0.68, P = 0.09; mPFS 4.0 vs 1.4 months, HR = 0.53, P < 0.01; ORR 14% vs 2%, P < 0.05). A treatment benefit was observed for patients with not CR/PR/SD when treated with nal IRI+5-FU/LV (n = 59) vs 5-FU/LV (n = 58) (mOS 6.1 vs 3.6 months, HR = 0.63, P = 0.04; mPFS 3.3 vs 1.6 months, HR = 0.56, P < 0.01; ORR 19% vs 0%, P < 0.01). Conclusion: In both the overall ITT NAPOLI-1 population and the nal-IRI+5-FU/LV arms, there was a trend towards improved efficacy outcomes in patients with CR/PR vs not CR/PR, however this trend was not observed in CR/PR/SD vs not CR/PR/SD patients. Patients in all treatment response subgroups benefited from treatment with nal-IRI+5-FU/LV vs 5-FU/LV, regardless of best response to prior therapy.