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Nab-paclitaxel plus gemcitabine may benefit some patients with surgically resected pancreatic cancer
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CHICAGO — The addition of nab-paclitaxel to gemcitabine did not significantly extend DFS per independent reviewer assessment among patients with surgically resected pancreatic cancer, according to results of the randomized phase 3 APACT trial presented at ASCO Annual Meeting.
However, the combination appeared to improve OS and DFS according to investigator assessment compared with gemcitabine alone at this interim analysis, and it may be a treatment option for select patients.
“The rationale to conduct this study was the results of the MPACT trial, which showed a clinically significant survival improvement of gemcitabine plus nab-paclitaxel in metastatic disease,” Margaret A. Tempero, MD, director of UCSF Pancreas Center, leader of the Pancreas Cancer Program and professor of medicine in the division of hematology and oncology at UCSF, told HemOnc Today.
In that trial, median OS was 8.7 months with the combination vs. 6.6 months with gemcitabine alone for patients with metastatic pancreatic cancer (P < .001).
In the multicenter, international, open-label APACT trial, Tempero and colleagues evaluated the efficacy of the combination among 866 treatment-naive patients (median age, 64 years; range, 34-86; 56% men) with histologically confirmed pancreatic cancer, macroscopic complete resection and an ECOG performance status of 0 (60%) to 1 (40%). Seventy-two percent of patients were lymph node positive.
Treatment — initiated within 12 weeks post-surgery — included 1,000 mg/m2 gemcitabine alone or with 125 mg/m2 nab-paclitaxel on days 1, 8 and 15 of six 28-day cycles.
DFS as assessed by an independent reviewer served as the study’s primary endpoint. Secondary endpoints included OS and safety.
“The original primary endpoint was OS, but we worked with the FDA to change to DFS to get the results earlier in order to get this treatment more quickly to patients,” Tempero said, adding that this is the first adjuvant trial in pancreatic ductal adenocarcinoma to use independently assessed DFS as the primary endpoint.
Sixty-nine percent of patients completed all six treatment cycles, including 66% of those on the combination arm and 71% of those assigned gemcitabine alone.
Median follow-up was 38.5 months.
Based on 439 events, median independent reviewer-assessed DFS was 19.4 months with the combination vs. 18.8 months with gemcitabine alone (HR = 0.88; 95% CI, 0.72-1.06), which did not represent a significant improvement.
However, investigator-assessed DFS — based on 571 events — showed significant improvement with the combination, at 16.6 months, vs. 13.7 months with gemcitabine alone (HR = 0.82; 95% CI, 0.69-0.96).
Based on 427 events, interim OS was 40.5 months with nab-paclitaxel and gemcitabine compared with 36.2 months with gemcitabine alone (HR = 0.82; 95% CI, 0.68-0.99).
Given the study did not meet its primary endpoint, despite a significant improvement in OS, whether these results will impact clinical practice is “complicated,” Tempero told HemOnc Today.
“The primary endpoint was independently assessed DFS by radiologist who did not have access to clinical data,” she said. “Radiographic postsurgical changes are sometimes difficult to distinguish from local recurrence. Investigator-assessed DFS tracked more closely with OS.”
Grade 3 or worse treatment-emergent adverse events occurred among more patients assigned the combination than gemcitabine alone (86% vs. 68%). The most common of these included neutropenia (49% vs. 43%) and fatigue (10% vs. 3%).
Two patients in each arm experienced a fatal treatment-emergent adverse event.
Until OS data mature, this combination may be an option for a select group of patients.
“Our OS data are immature, and we expect the results to strengthen over time,” Tempero said. “In the meantime, further investigation is needed in high-risk patients and in those who are not candidates for FOLFIRINOX.” – by Alexandra Todak
Reference:
Tempero MA, et al. Abstract 4000. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Tempero reports consultant/advisory roles with, or research funding and travel expenses from, AbbVie, Advance Medical, Astellas Pharma, AstraZeneca, BioPharm Communications, Bristol-Myers Squibb, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Igyta, Immunovia, Merck, Pharmacyclics, Pharmcyte Biotech and Tocagen. Please see the abstract for all other authors’ relevant financial disclosures.