CHICAGO – While gemcitabine plus nab-paclitaxel did not extend independently assessed disease-free survival versus gemcitabine alone in a phase 3 pancreatic cancer study, overall survival data are “encouraging” thus far, and merit further follow-up, an investigator said at the annual meeting of the American Society of Clinical Oncology.
The APACT trial was the first adjuvant pancreatic cancer trial to use an endpoint of disease-free survival, independently assessed without knowledge of medical or clinical circumstances, said investigator Margaret A. Tempero, MD, director of the UCSF Pancreas Center, San Francisco.
With that specific method of assessment, median disease-free survival was 19.4 months for gemcitabine plus nab-paclitaxel versus 18.8 months for gemcitabine alone, a finding that had a “slight trend” in favor of the combination arm, Dr. Tempero said.
By contrast, a more standard investigator-assessed disease-free survival showed an improvement favoring gemcitabine plus nab-paclitaxel over gemcitabine alone, in line with preliminary overall survival data that also appear to show an advantage for the combination over gemcitabine, according to Dr. Tempero.
“We thought we were introducing more rigor into the trial, but I think we all recognize clinically that it is often difficult to differentiate or distinguish recurrence in the pancreatic bed from postsurgical changes,” she said in a discussion period, “but clearly, this is a lesson learned, and I think that would be helpful for the field going forward in avoiding that endpoint.”
Since the trial was launched, both modified FOLFIRINOX and gemcitabine plus capecitabine have become category 1 recommendations for adjuvant pancreatic cancer in clinical practice guidelines from the National Comprehensive Cancer Network.
The “jury is still out” on whether gemcitabine plus nab-paclitaxel will join that group, said Jiping Wang, MD, PhD, of Dana-Farber Cancer Institute, Boston, who discussed the results of the APACT trial in a podium presentation.
“We are still waiting for the final overall survival result of the APACT trial,” he said. “Hopefully, the nab-paclitaxel/gemcitabine combination provides an alternative treatment, especially for patients with R1 resection who cannot tolerate modified FOLFIRINOX.”
While gemcitabine plus capecitabine is a good choice for patients who aren’t able to tolerate modified FOLFIRINOX, available evidence suggests it may not benefit patients with R1 resection, according to Dr. Wang.
The phase 3 APACT trial included patients with surgically resected pancreatic cancer enrolled at 179 sites in 21 countries. A total of 866 patients were randomized 1:1 to receive gemcitabine plus nab-paclitaxel or gemcitabine alone for six cycles.
While median independently assessed disease-free survival was 19.4 months for gemcitabine/nab-paclitaxel and 18.8 months for gemcitabine (hazard ratio, 0.88; P = .1824), median investigator-assessed disease free survival was 16.6 months versus 13.7 months for those arms, respectively (HR, 0.82; P = .0168), according to reported results.
Median interim overall survival was 40.5 months for gemcitabine/nab-paclitaxel versus 36.2 months for gemcitabine (HR, 0.82; P = .045), though the presenter emphasized that longer follow-up is needed to clarify the role of this combination as adjuvant therapy for pancreatic adenocarcinoma.
“I don’t think it’s wrong in a patient who can’t tolerate modified FOLFIRINOX to use gemcitabine and nab-paclitaxel, but I’m not sure everybody would agree with that,” Dr. Tempero said after being asked in the study discussion period if she would advocate for use of this combination regimen in frail patients.
“I think when we get more mature overall survival data, it will be a lot easier to make those decisions,” she said.
Dr. Tempero reported disclosures related to Abbie, Advance Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, BioPharm Communications, Celgene, CPRIT, EcoR1 Capital, Eisai, FibroGen, Halozyme, Ignyta, Immunovia, Merck, Pharmacyclics, Pharmacyte Biotech, and Tocagen.
SOURCE: Tempero MA, et al. ASCO 2019. .