Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P + Gem) vs gemcitabine (Gem) alone in patients with resected pancreatic cancer (PC): Updated 5-year overall survival

Background The APACT trial evaluated the safety and efficacy of adjuvant nab -P + Gem vs Gem alone in patients with resected PC. Between April 2014 and April 2016, 866 patients were randomized. As previously reported, APACT did not meet the primary endpoint of independently assessed disease-free survival (DFS); however, the prespecified sensitivity analysis for median investigator-assessed DFS was 16.6 months with nab -P + Gem and 13.7 months with Gem (HR, 0.82; 95% CI, 0.694–0.965; nominal P=0.0168). The overall survival (OS; secondary endpoint) at the time of the primary analysis trended in favor of nab -P + Gem: median 40.5 vs 36.2 months (427 events; 68% mature; HR, 0.82; 95% CI, 0.680–0.996; nominal P=0.045). The post hoc updated follow-up survival analysis outcomes were consistent with those observed in the primary analysis of nab -P + Gem vs Gem: median 41.8 vs 37.7 months (511 events; 81% mature; HR, 0.82; 95% CI, 0.687–0.973; nominal P=0.0232). Safety outcomes as previously presented were consistent with those reported in the treated population for the entire trial. Here, we present updated 5-year OS in the intent-to-treat population. Trial design Treatment-naive patients with histologically confirmed pancreatic adenocarcinoma, macroscopic complete resection (R0 or R1), Eastern Cooperative Oncology Group performance status 0 or 1, and carbohydrate antigen 19-9 levels < 100 U/mL were eligible. Stratification factors were resection status (R0 vs R1), lymph node status (positive vs negative) and region (North America, Europe, and Australia vs. Asia Pacific). Treatment was initiated ≤12 weeks postsurgery. Patients received nab-P 125 mg/m2 + Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of six 28-day cycles. The primary endpoint was DFS by independent review. Secondary endpoints were OS and safety. Methods Treatment-naive patients with histologically confirmed pancreatic adenocarcinoma, macroscopic complete resection (R0 or R1), Eastern Cooperative Oncology Group performance status of 0 or 1, and carbohydrate antigen 19-9 levels nab -P 125 mg/m2 + Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of six 28-day cycles. The primary endpoint was DFS by independent review. Secondary endpoints were OS and safety. Results As of the data cutoff date (9 April 2021), all patients had been followed up for ≥5 years or discontinued from the study. The median follow-up time for OS was 63.2 months. In the intent-to-treat population, 268 and 287 events occurred in the nab -P + Gem and Gem arms, respectively (88% mature). The median OS in the nab -P + Gem arm was 41.8 months compared with 37.7 months in the Gem arm (HR, 0.80; 95% CI, 0.678–0.947; nominal P=0.0091). Five-year OS rates were 38% with nab -P + Gem and 31% with Gem. Patterns of OS in the prespecified subgroups were generally consistent with observations from the intent-to-treat population: R0 (HR, 0.85; 95% CI, 0.698–1.034); R1 (HR, 0.73; 95% CI, 0.534–1.003); LN+ (HR, 0.77; 95% CI, 0.636–0.922); LN− (HR, 0.97; 95% CI, 0.667–1.415). Conclusions The 5-year OS outcomes in the APACT trial were consistent with those observed in both the primary analysis and the prior post hoc updated analysis for nab -P + Gem vs Gem alone. Although APACT did not meet its primary endpoint of independently assessed DFS in the primary analysis, these OS data suggest improved outcomes with nab -P + Gem. Clinical trial identification EudraCT (2013-003398-91) and ClinicalTrials.gov (NCT01964430). Editorial acknowledgement Writing assistance was provided by Krystin Tran, PharmD, of Chrysalis Medical Communications, Ltd, and funded by Bristol Myers Squibb Company. The authors are fully responsible for all content and editorial decisions for this abstract. Legal entity responsible for the study Bristol Myers Squibb. Funding Sponsorship of this study was funded by Bristol Myers Squibb Company. Disclosure M. Tempero: Advisory / Consultancy: AstraZeneca, Bristol-Meyers Squibb, FibroGen Research grant / Funding (institution): Celgene, Halozyme. E. O'Reilly: Advisory / Consultancy: Cytomx Therapeutics (DSMB), Rafael Therapeutics (DSMB), Sobi, Silenseed, Tyme, Seagen, Molecular Templates, Boehringer Ingelheim, BioNTech, Ipsen, Polaris, Merck, AstraZeneca, Noxxon Research grant / Funding (institution): Genentech/Roche, Celgene/BMS, BioNTech, BioAtla, AstraZeneca, Arcus, Elicio, Parker Institute, AstraZeneca Spouse / Financial dependant: Celgene-BMS, Bayer, Genentech-Roche, Eisai. E. Van Cutsem: Advisory / Consultancy: Bayer, Lilly, Roche, Servier, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Halozyme, Array BioPharma, Biocartis, GlaxoSmithKline, Daiichi Sankyo, Pierre Fabre, Sirtex Medical, Taiho Pharmaceutical, Incyte. Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. J. Berlin: Advisory / Consultancy: Rafael Research grant / Funding (institution): BMS. J. Tabernero: Honoraria (self): educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Advisory / Consultancy: Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc. M. Borad: Research grant / Funding (institution): Celgene. J. Bachet: Honoraria (self): Servier, Amgen, Merck Serono, Sanofi, Roche, Pierre Fabre Advisory / Consultancy: Servier, Amgen, Merck Serono, Pierre Fabre Travel / Accommodation / Expenses: Servier, Amgen, Merck Serono, Sanofi, Roche. N. Tebbutt: Advisory / Consultancy: Bristol Myers Squibb. G. Zhang: Full / Part-time employment: Bristol Myers Squibb. D. McGovern: Shareholder / Stockholder / Stock options: Bristol Myers Squibb Full / Part-time employment: Bristol Myers Squibb. H. Marks: Full / Part-time employment: Bristol Myers Squibb. A. Biankin: Advisory / Consultancy: BMS, AstraZeneca, MyTomorrows, Elstar Therapeutics Leadership role: Cumulus Oncology, Modulus Oncology, Wollemia Oncology, concur, Cambridge Cancer Genomics, Gabrial Precision Oncology, human.ai Research grant / Funding (institution): BMS, AstraZeneca, MyTomorrows, Elstar Therapeutics Shareholder / Stockholder / Stock options: Cumulus Oncology, Modulus Oncology, Wollemia Oncology, concur, Cambridge Cancer Genomics, Gabrial Precision Oncology, human.ai Licensing / Royalties: Agilent Technologies. All other authors have declared no conflicts of interest.