5-Year OS Data Favor Nab-Paclitaxel With Gemcitabine Over Gemcitabine Alone for Resected Pancreatic Cancer

Margaret A. Tempero, MD

Treatment with nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer showed positive 5-year overall survival (OS) outcomes that were consistent with the primary analysis of the phase 3 APACT clinical trial (NCT01964430) as well as a post hoc analysis.

During a presentation given during the ESMO World Congress on Gastrointestinal Cancer by Margaret A. Tempero of UCSF Helen Diller Family Comprehensive Cancer Center, it was suggested that although the study missed its primary end point of disease-free survival (DFS) improvement, the OS benefit observed signifies promise for the combination as treatment of resected pancreatic cancer.

APACT is phase 3, multicenter, international, open-label, randomized trial that assessed the safety and efficacy of nab-paclitaxel in combination with gemcitabine compared with gemcitabine alone in the resected pancreatic cancer patient population. A total of 866 patients were enrolled and randomized 1:1 to receive nab-paclitaxel at 125 mg/m² every 3 or 4 weeks in combination with gemcitabine 1000 mg/m² every 3 or 4 weeks for 6 cycles, in the experimental arm or the same dose of gemcitabine as monotherapy in the control arm.

Randomization in the study occurred as soon as possible following resection and no later than 12 weeks after. All therapies administered to patients were continued until disease recurrence, death, unacceptable toxicity, withdrawal of consent, or patient or physician decision.

Patients were required to be at least 18 years old to be included in the study and have a confirmed R0/R1 resected pancreatic tumor, an ECOG performance status of 0 or 1, CT with evidence of disease, CA19-9 < 100 U/mL, and be treatment naïve. For assessment, patients were stratified by resection status, lymph node status, and region.

The secondary end points of the study were OS and safety. The investigators also looked at exploratory end points, including molecular profiling of tumor tissue, blood tests to identify tumor nucleic acids, and quality of life.

The primary analysis showed a median DFS of 16.6 months in the combination arm versus 13.7 months in the gemcitabine-only arm (HR, 0.82; 95% CI, 0.694-0.965; P =.0168). The median OS observed during the primary analysis was 40.5 months with nab-paclitaxel plus gemcitabine versus 36.2 months with gemcitabine alone (HR, 0.82; 95% CI, 0.680–0.996; P =.045). The post hoc analysis showed a median OS of 41.8 months for the nab-paclitaxel plus gemcitabine combination versus 37.7 months for gemcitabine alone (HR, 0.82; 95% CI, 0.687–0.973); P = 0.023).

The initial safety assessment of the combination versus gemcitabine alone showed that the most frequent grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia (49% vs 43%), anemia (15% vs 8%), and fatigue (10% vs 3%). The combination arm also showed a 15% incidence of grade 3 or higher peripheral neuropathy but no cases of this AE were observed in the gemcitabine-alone arm.

Follow-up in the study for radiological evaluation was 5 years or more after the final dose of study treatment or until recurrence, new cancer therapy, or death. The safety evaluations were conducted for 28 days after the final dose of therapy. The data cutoff date for the 5-year OS analysis was April 9, 2021, and as of that date, all patients in the study had been followed for 5 years or more or were discontinued from the study.

Baseline characteristics for the 5-year OS population showed that the median age was 64.0 years (range, 34-83) for the combination arm compared with 64.0 years (range, 38-86) for the monotherapy arm. More than half of the overall study population was male.

In terms of clinical characteristics observed at baseline, most patients, including 58% of the experimental arm versus 62% of the control arm had an ECOG performance status of 0. Seventy-six percent of the nab-paclitaxel and gemcitabine arm had a tumor-free margin compared with 77% of the gemcitabine-alone arm. The remaining patients had an R1 resection status. Node status was positive for 72% of the combination arm and 72% of the monotherapy arm.

The baseline CA19-9 was a median of 14.31 U/mL (range, 1.00-255.28) among patients in the combination arm compared with 12.90 U/mL (range, 1.00-275.87) in the single-agent arm). The tumor stage at baseline was T3 for most patients and the distance from the closets margin was at least 1mm for 66% of the experimental arm versus 67% of the control group.

At a median follow-up of 63.2 months, the 5-year OS rate was 38% among patients treated with nab-paclitaxel plus gemcitabine versus 31% for those treated with gemcitabine alone (HR, 0.8; 95% CI, 0.678-0.947; nominal P =.0091). There was a total of 555 OS events and the data had reached 88% maturity.

When stratified by resection status, OS favored the nab-paclitaxel/gemcitabine combination compared with gemcitabine monotherapy for both the R0 and R1 patients (HR, 0.85; 95% CI, 0.698-1.034) and (HR, 0.73; 95% CI, 0.534-1.003), respectively. When patients were stratified by lymph node status, those who were node-positive had longer OS when treated with the experimental combination as did those with node-negative disease. Finally, patients from all regions including North America, Europe, Australia, and the Asia Pacific region had prolonged OS when treated with nab-paclitaxel combined with gemcitabine versus those who only received gemcitabine.

_Reference:

_{Tempero MA, O’Reilly EM, Cutsem EV, et al. Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone in patients with resected pancreatic cancer: updated 5-yearoverall survival. Presented at: ESMO World Congress on Gastrointestinal Cancers 2021; June 30–July 2, 2021. Abstract LBA-1.}