Nab-paclitaxel Plus Gemcitabine Boosts Survival for Pancreatic Cancer in 5-year Follow-Up

Margaret A. Tempero, MD

Updated overall survival (OS) data from the APACT trial (NCT01964430) suggest improved outcomes for patients with resected pancreatic cancer who receive adjuvant nab-paclitaxel (Abraxane) plus gemcitabine despite missing the primary end point in earlier analysis.¹

Investigators selected disease-free survival (DFS) as the primary objective of the study, making it the first adjuvant pancreatic cancer trial to use the independently assessed marker.² The interim analysis of OS was reported in 2019 and demonstrated early signs of efficacy for the combination regimen compared with gemcitabine alone.

In a presentation of the data at the 2019 American Society of Clinical Oncology Annual Meeting, lead investigator Margaret A. Tempero, MD, said, “the overall survival [data] is encouraging and longer follow-up will clarify the role for this combination as adjuvant therapy for [patients with] pancreatic adenocarcinoma.” Tempero added that based on the early data, investigators should consider exploring the regimen in patients with lymph node–positive disease, R1 resection, or an inability to tolerate modified FOLFIRINOX.¹

Tempero presented the updated OS analysis was reported as part of the 2021 European Society for Medical Oncology Virtual World Congress on Gastrointestinal Cancer. At the 5-year data cutoff, the OS outcomes were consistent with those observed in the primary analysis and a prior post hoc update analysis. At a median follow-up of 63.2 months, the median OS for patients in the nab-paclitaxel plus gemcitabine was 41.8 months compared with 37.7 months in the gemcitabine cohort (HR, 0.80; 95% CI, 0.678-0.947; P = .0091).¹ Further, the 5-year OS rates were 38% and 31%, respectively.

Investigators noted that a survival benefit was observed across all subgroups and was consistent with observations in the intention-to-treat population. When stratified by resection status, OS favored the nab-paclitaxel plus gemcitabine combination compared with gemcitabine monotherapy for patients with R1 disease (HR, 0.73; 95% CI, 0.534-1.003). Additionally, a greater benefit was observed for those with lymph node positive status (HR, 0.77; 95% CI, 0.636-0.922) compared with those with lymph node negative status (HR, 0.97; 95% CI, 0.667-1.415).

“Although APACT did not meet its primary end point of independently assessed DFS in the primary analysis, these OS data suggest improved outcomes with nab-paclitaxel plus gemcitabine,” Tempero said of the updated data. Tempero is a 2020 Giant of Cancer Care® award winner in the gastrointestinal cancers category and is the Rombauer Family Distinguished Professorship in Pancreas Cancer Clinical and Translational Science, director, of the University of California, San Francisco (UCSF) Pancreas Center, leader of the Pancreas Cancer Program and a professor of medicine at the UCSF Helen Diller Family Comprehensive Cancer Center.

Rationale and Study Design

Results of the phase 3 MPACT trial (NCT00844649) demonstrated significantly longer OS with nab-paclitaxel plus gemcitabine compared with gemcitabine alone for patients with metastatic pancreatic cancer, which led to the approval of the combination in 2013. Investigators determined that a similar benefit may be observed with the combination over gemcitabine alone, anticipating a DFS of 18.5 months vs 13.5 months.¹

The 2019 analysis demonstrated a median independently assessed DFS of 19.4 months with the the addition of nab-paclitaxel vs 18.8 months with gemcitabine alone (HR, 0.88; 95% CI, 0.729-1.063; P = .1824). Investigator-assessed analysis aligned more closely with the reported OS analysis and the hypothesized outcomes (TABLE^1,2). Specifically, investigator assessed DFS results were 16.6 months with the combination vs 13.7 months with gemcitabine (HR, 0.82; 95% CI, 0.694-0.965; P = .0168). At the time of presentation, Tempero noted that the concordance rate between disease recurrence by independent radiological review and by investigator review was 77%.¹

Per APACT trial protocol, patients with surgically resected pancreatic adenocarcinoma were randomized to receive either nab-paclitaxel plus gemcitabine (n = 432) or gemcitabine alone (n n = 434) and radiographic evaluation took place for 5 years of follow-up following the last dose of treatment or until recurrence, commencement of new cancer therapy, or death. Data cutoff for OS analysis was April 9, 2021, at which time all patients had been followed up for at least 5 years or had discontinued from the study.²

Nab-paclitaxel was administered intravenously (IV) at 125 mg/m2 on days 1, 8, and 15 of a 28-day cycle and IV gemcitabine at 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle for a total 6 cycles. Gemcitabine was administered at the same dose and same schedule in the monotherapy arm. Overall, 69% of patients completed 6 treatment cycles; 287 patients (66%) completed treatment with the combination and 310 (71%) completed treatment with gemcitabine alone.

To be eligible for enrollment, patients had to have histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection and pancreatic cancer surgical staging of T 1 to 3, N0 to N1, M0 disease. Patients must have been able start treatment no later than 12 weeks following surgery and be age at least 18 years at the time of signed consent. Further, patients must have had a CT scan without evidence of disease and have CA19-9 levels of less than 100 U/mL assessed within 14 days of randomization.

Those who received prior neoadjuvant treatment or radiation therapy, had metastatic disease, had any other malignancy within 5 years of randomization, had an active infection requiring systemic therapy, and/or had known hepatitis B or C infection or HIV infection were excluded.

Baseline characteristics were well balanced between the arms with a median age of 64 years (range, 34-86), many having a resection status of R0 (76%) indicating a reported tumor-free margin, and most patients having positive lymph nodes (72%). Median baseline CA19-9 levels were reported as 13.65 U/mL.

TABLE: Updated Survival Outcomes in APACT Trial^1,2

References

1. Tempero MA, O’Reilly E, Van Cutsem E, et al. 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. Ann Oncol. 2021;32(suppl 3):S226. doi:10.1016/j.annonc.2021.06.009
2. Tempero MA, Reni M, Riess H, et al. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol. 2019;37(suppl 15):4000. doi:10.1200/JCO.2019.37.15_suppl.4000