NAPOLI-1 phase III trial outcomes by prior surgery, and disease stage, in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) (2018)

Background: The NAPOLI-1 phase 3 trial (NCT01494506) reported significantly increased median OS with nal-IRI+5-FU/LV vs 5-FU/LV (6.1 mo vs 4.2 mo; HR = 0.67; p = 0.012) in mPDAC patients who progressed after gemcitabine-based therapy. We report subgroup analysis outcomes in NAPOLI-1 patients who had undergone prior surgery and by disease stage at diagnosis. Methods: This post-hoc analysis investigated outcomes with or without prior surgery, and by disease stage at diagnosis (stage IIA, IIB, or III, vs IV). P values are descriptive. Results: In the NAPOLI-1 trial, OS and PFS were increased in ITT patients who had undergone prior surgery compared to those who did not (Table). In patients with prior surgery receiving nal-IRI+5-FU/LV (n = 40), OS and PFS were increased vs 5-FU/LV (n = 43) (HR = 0.84 and 0.72). Patients without prior surgery had significantly increased OS and PFS with nal-IRI+5-FU/LV (n = 77) vs 5-FU/LV (n = 76) (HR = 0.56, p = 0.003 and HR = 0.47, p < 0.001). OS was significantly increased in ITT patients with disease stages IIA (n = 36, HR = 0.59, p = 0.013), IIB (n = 77, 0.54, <0.001), and III (n = 75, 0.57, <0.001) vs stage IV (n = 213). A consistent OS increase was also seen in patients treated with nal-IRI+5-FU/LV: stage IIA (HR = 0.63, ns) stage IIB (HR = 0.50, p = 0.024) and stage III (HR = 0.43, p = 0.021) vs stage IV. Conclusions: OS and PFS were increased in ITT patients who had undergone surgery prior to trial inclusion. Patients treated with nal-IRI+5-FU/LV showed a consistent increase in OS and PFS vs 5-FU/LV. ITT patients with stages IIA, IIB, and III had significantly improved OS vs those with stage IV disease. Treatment with nal-IRI+5-FU/LV showed a survival benefit across disease stages IIA, IIB, and III, vs stage IV. Limited patient numbers should be taken into consideration when interpreting these findings.Table: 733PPrior surgeryAll ITTYes*Comparing treatments;No*Comparing treatments;Yesn=142Non=275nal-IRI+5-FU/LVn=405-FU/LVn=43nal-IRI+5-FU/LVn=775-FU/LVn=76mOS6.84.48.46.15.33.4HR,0.620.840.56P value<0.0010.5470.003mPFS2.62.22.82.63.31.4HR,0.840.720.47P value0.1290.217<0.001Disease stage at diagnosisStage IIAStage IIBAll ITTnal-IRI+5-FU/LV5-FU/LVAll ITTnal-IRI+5-FU/LV5-FU/LVn = 36n = 6n = 9n = 77n = 26n = 22mOS6.48.66.16.110.25.6HR,†vs Stage IV0.590.630.420.540.500.43P value0.0130.3900.070<0.0010.0240.012Stage IIIStage IVAll ITTnal-IRI+5-FU/LV5-FU/LVAll ITTnal-IRI+5-FU/LV5-FU/LVn = 75n = 21n = 19n = 213n = 61n = 62mOS6.39.07.04.24.73.1HR,†vs Stage IV0.570.430.49---P value<0.0010.0210.039* Comparing treatments;† vs Stage IV Open table in a new tab Clinical trial identification: NCT01494506. Editorial acknowledgement: Medical writing support for the preparation of this abstract was provided by Physicians World Europe GmbH, Mannheim, Germany, with financial support from Shire (previously Baxalta), Zug, Switzerland. Legal entity responsible for the study: Merrimack Pharmaceuticals. Funding: The analysis was funded by Shire, the study was funded by Merrimack Pharmaceuticals. Disclosure: G. Bodoky: Consulting, Advisory role: Bayer, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche; Support for travel, accommodation and expenses: Janssen, Lilly, Novartis, Pfizer, Roche. J. Siveke: Consulting, Advisory role: Merrimack Pharmaceuticals, Baxalta (now part of Shire), Celgene, Lilly; Research funding: Celgene, Bristol-Myers Squibb, 4SC, Novartis, Boehringer Ingelheim; Travel, accommodation, expenses: Roche, Celgene, Shire. J. Chen, F. de Jong: Employee, Stockholder: Shire. B. Mirakhur: Employee: Ipsen, Stockholder: Ipsen, GlaxoSmithKline. A. Dean: Honoraria: Specialised Therapeutics Australia; Consultant/Advisor: Baxalta (now part of Shire), Celgene. L-T. Chen: Honoraria, Consultant, Advisor: Bristol-Myers Squibb, Ono Pharmaceutical, Lilly, MSD, PharmaEngine, Merrimack Pharmaceuticals, TTY Biopharm, SynCoreBio, Five Prime, Novartis; Patent: Hunilife Technology; Research funding: Novartis, GlaxoSmithKline, Merck Serono, TTY Biopharm, Polaris, SyncoreBio, Pfizer, Celgene. All other authors have declared no conflicts of interest.