The 5-year outcomes in the APACT trial uphold the overall survival benefit with nab-paclitaxel plus gemcitabine in the adjuvant treatment of patients with resected pancreatic cancer, according to Margaret A. Tempero, MD, Director of the University of California San Francisco Pancreas Center, who presented the update at the 2021 ESMO World Congress on Gastrointestinal Cancer.1
Dr. Tempero presented the 5-year overall survival data for the intent-to-treat population of 866 patients, with a data cutoff of April 9, 2021, and a median follow-up of 63.2 months. All patients had been followed for at least 5 years or had discontinued the study. The data are considered 88% mature, with 555 overall survival events having occurred.
With nab-paclitaxel/gemcitabine, median overall survival was 41.8 months vs 37.7 months with gemcitabine alone (hazard ratio [HR] = 0.80; P = .0091). The 5-year overall survival rates were 38% vs 31%, she reported.
Although APACT did not meet its primary endpoint of independently assessed disease-free survival in the primary analysis, these overall survival data suggest improved outcomes with nab-paclitaxel plus gemcitabine.— Margaret A. Tempero, MD
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“Although APACT did not meet its primary endpoint of independently assessed disease-free survival in the primary analysis, these overall survival data suggest improved outcomes with nab-paclitaxel plus gemcitabine,” Dr. Tempero said. “The 5-year overall survival outcomes were consistent with those observed in both the primary analysis and the prior post hoc updated analysis for nab-paclitaxel plus gemcitabine vs gemcitabine alone.”
In the previously reported primary analysis, overall survival—a secondary endpoint—trended in favor of nab-paclitaxel/gemcitabine, with median overall survival of 40.5 months vs 36.2 months, respectively (HR = 0.82; P = .045).2 In the post hoc updated analysis, this comparison was 41.8 months vs 37.7 months (HR = 0.82; P = .023).3
Patterns of overall survival in the prespecified subgroups were generally consistent with observations from the intent-to-treat population, she said.
APACT Details
APACT was a phase III international open-label randomized trial that evaluated nab-paclitaxel plus gemcitabine vs gemcitabine alone in patients with resected pancreatic cancer. It is one of several trials evaluating the benefit of adjuvant therapy. After the launch of APACT, gemcitabine plus capecitabine and modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) demonstrated survival benefits in the adjuvant ESPAC-44 and PRODIGE-24 trials5 and therefore became preferred treatments.
The global study enrolled 866 treatment-naive patients who had undergone macroscopic complete resection. Most were lymph node–positive (72%) and had R0 resections (76%), and all patients showed no evidence of persistent disease.
Patients were randomly assigned to receive, within 12 weeks of surgery, nab-paclitaxel at 125 mg/m2 plus gemcitabine at 1,000 mg/m2 or gemcitabine alone at 1,000 mg/m2 on days 1, 8, and 15 of six 28-day cycles. The primary endpoint was radiologic disease-free survival, independently assessed without reviewers’ knowledge of clinical circumstances.
Primary Endpoint: No Difference in Disease-Free Survival
As previously reported, APACT did not meet its primary endpoint of independently assessed disease-free survival. However, the prespecified sensitivity analysis for investigator-assessed disease-free survival appeared to align more closely with the overall survival results, favoring the combination.2 Hazard ratios for disease-free survival were 0.88 (P = .1824) by independent assessment and 0.82 (P = .0168) by investigator assessment. Median disease-free survival was 19.4 vs 18.8 months and 16.6 vs 13.7 months, respectively.
Many experts questioned the use of independently assessed disease-free survival as the primary endpoint after Dr. Tempero’s first presentation of the APACT data. At that time, Dr. Tempero explained and commented: “We all recognize that, clinically, it’s often difficult to distinguish recurrence in the pancreatic bed from postsurgical changes. Independent assessment had never been used before, and we thought we were introducing more rigor into the trial. Clearly, this is a lesson learned for the field going forward: avoid this endpoint.”
DISCLOSURE: Dr. Tempero has served as a consultant or advisor to AbbVie, Advance Medical Teledoc Health, AstraZeneca, Bristol Myers Squibb, EcoR1 Capital, Eisai, Elicio Therapeutics, FibroGen, GlaxoSmithKline, Immunovia, Ipsen, Karyopharm Therapeutics, Merck & Co, Pharmacyclics LLC, and Swedish Orphan Biovitrum; has received institutional research funding from Celgene and Halozyme; and has been reimbursed for travel, accommodations, or other expenses by AbbVie, AstraZeneca, BioPharm Communications, Bristol Myers Squibb, Eisai, GlaxoSmithKline LLC, Merck, Pharmacyclics LLC, PharmaCyte Biotech, and Tocagen.
REFERENCES
1. Tempero M, O’Reilly E, Van Cutsem E, et al: Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone in patients with resected pancreatic cancer: Updated 5-year overall survival. 2021 ESMO World Congress on Gastrointestinal Cancer. Abstract LBA-1. Presented June 30, 2021.
2. Tempero MA, Reni M, Riess H, et al: APACT: Phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine for surgically resected pancreatic adenocarcinoma. 2019 ASCO Annual Meeting. Abstract 4000. Presented June 2, 2019.
3. Reni M, Riess H, O’Reilly EM, et al: Phase III APACT trial of adjuvant nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with resected pancreatic cancer: Outcomes by geographic region. 2020 ASCO Annual Meeting. Abstract 4515. Presented May 25, 2020.
4. Neoptolemos JP, Palmer DH, Ghaneh P, et al: Comparison of adjuvant gemcitabine plus capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicenter, open-label, randomized phase 3 trial. Lancet 389:1011-1024, 2017.
5. Conroy T, Hammet P, Hebbar M, et al: Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine in patients with resected pancreatic ductal adenocarcinomas. 2018 ASCO Annual Meeting. Abstract LBA4001. Presented June 4, 2018.
