Induction chemotherapy with nab-paclitaxel plus gemcitabine or sequential FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) followed by surgical exploration induced high conversion rates in patients with locally advanced pancreatic cancer, and conversion was associated with improved overall survival, according to final results from the NEOLAP study that were presented by Kunzmann et al at the European Society for Medical Oncology (ESMO) Congress 2019 (Abstract 671O).

Volker Kunzmann, MD, of the University Hospital Wuerzburg and Comprehensive Cancer Centre Mainfranken, presented the final results from the first prospective, randomized trial comparing the efficacy and safety of either nab-paclitaxel plus gemcitabine or sequential FOLFIRINOX as induction chemotherapy in locally advanced pancreatic cancer.

Approximately 30% of patients with pancreatic cancer present with locally advanced tumors, and multiagent induction chemotherapy is recommended for this situation, but the optimal regimen is unknown. Conversion to resectable tumors in locally advanced pancreatic cancer after chemotherapy and/or radiotherapy has been reported at variable frequencies in larger prospective multicenter trials, usually based on radiographic resectability criteria.

Methods

Dr. Kunzmann and colleagues conducted an open-label, randomized, two-arm, phase II trial in 168 treatment-naive patients with histologically and/or cytologically confirmed nonresectable locally advanced pancreatic cancer recruited from 33 German centers.

Patients received two cycles of nab-paclitaxel/gemcitabine induction; following these treatment cycles, 130 patients without progressive disease or unacceptable adverse events were randomly assigned 1:1 to receive either two additional cycles of nab-paclitaxel/gemcitabine (n = 64) or four cycles of unmodified sequential FOLFIRINOX (n = 66).

Secondary resectability was assessed by surgical exploration in all patients achieving stable disease or a response after completion of induction chemotherapy. Complete macroscopic tumor resection (R0/R1 resection) was the primary endpoint of the trial. Secondary endpoints included safety, overall response rate, disease control rate (DCR), CA 19-9 response, pathologic response, recurrence-free survival, progression-free survival, and overall survival.

Results

The DCR was 82.3% in the nab-paclitaxel/gemcitabine group vs 75.0% in the sequential FOLFIRINOX group (P = .38).

Surgical exploration was possible in equivalent numbers of patients receiving each treatment, and was performed in 62.5% of patients in the nab-paclitaxel/gemcitabine group and 63.6% in the sequential FOLFIRINOX group.

The primary endpoint of the conversion rate was 30.6% with nab-paclitaxel/gemcitabine compared to 45.0% with sequential FOLFIRINOX (odds ratio = 0.54; 95% confidence interval (CI) = 0.26–1.13 (P =.135). Regarding the secondary efficacy endpoints, there was no difference between two groups. With a median follow-up of 13.8 months, the median overall survival was 17.2 months with nab-paclitaxel/gemcitabine compared to 22.5 months with sequential FOLFIRINOX (adjusted hazard ratio (HR) = 0.73; 95% CI = 0.42–1.28, P = .268).

Conversion was associated with significantly improved overall survival in the 165 patients in the intent-to-treat population; overall survival was 27.4 months in patients who converted compared to 14.2 months in those who did not (P = .0035).

The number of grade ≥ 3 adverse events were similar with the treatment arms—they were reported in 54.7% of patients in the nab-paclitaxel/gemcitabine group and in 53.0% of patients receiving sequential FOLFIRINOX.

According to the authors, sequential FOLFIRINOX was not significantly superior to 4-month induction chemotherapy with nab-paclitaxel/gemcitabine in terms of conversion rate as the study primary endpoint, as well as in terms of secondary efficacy endpoints. Both induction chemotherapy regimens were tolerable and consistent with their known safety profiles. However, secondary tumor resection after obligatory surgical exploration was associated with significant survival benefit and is therefore highly recommendable in patients with locally advanced pancreatic cancer. Results of ongoing central radiographic review in terms of resectability status and response rate, as well as translational biomarker analyses from this study will be presented at future meetings.

Disclosure: Funding for NEOLAP was provided by Celgene. For full disclosures of the study authors, visit esmo.org.