KEY TAKEAWAYS
- A Phase III trial was conducted to assess the efficacy and safety of combination therapy with nab-paclitaxel and gemcitabine compared to gemcitabine monotherapy for the treatment of resected pancreatic ductal adenocarcinoma.
- A total of 866 treatment-naïve patients were randomly assigned to either treatment arm.
- The Median independently assessed DFS was 19.4 months in the nab-paclitaxel + gemcitabine arm and 18.8 months in the gemcitabine arm (P=0.18).
- Median overall survival (OS) was 40.5 and 36.2 months, respectively (P=0.045).
- This Phase III trial showed an improved OS with combination therapy; however, the primary endpoint was not met.
Adjuvant nab-paclitaxel + gemcitabine was compared to gemcitabine for resected pancreatic ductal adenocarcinoma treatment in this randomized, open-label trial. Researchers randomly allocated 866 patients with pancreatic ductal adenocarcinoma who had never received any prior treatment to receive either nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone by a single 30- to 40-minute infusion on days 1, 8, and 15 of six 28-day cycles. Independent assessment of DFS (disease-free survival) was the primary outcome. Investigator-assessed DFS, OS (overall survival), and safety were additional end goals.
Of 432 patients treated with nab-paclitaxel + gemcitabine and 434 patients treated with gemcitabine alone, 287 and 310, respectively, achieved complete responses. Independently assessed median DFS was 19.4 months (nab-paclitaxel + gemcitabine) compared to 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P =.18) at primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR] 33.8-43 months]. Median DFS, as determined by the investigators, was 16.6 months (IQR, 8.4-47.0) and 13.7 months (IQR, 8.3-44.1) for both groups, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P =.02). Median overall survival (OS) was 40.5 (IQR, 20.7 to not reached) months and 36.2 (IQR, 17.7-53.3) months (HR, 0.82; 95% CI, 0.680 to 0.996; P =.045) for the 2 groups, respectively (427 occurrences; 68% mature).
Median overall survival (511 events; 81% adult) was 41.8 months (nab-paclitaxel + gemcitabine) against 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P =.0232) after 16 months of follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]). Median OS at 5 years of follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P =.0091; 555 events; 88% mature).
With nab-paclitaxel and gemcitabine, 86% of patients suffered grade ≥ 3 treatment-emergent adverse events, while with gemcitabine, 68% did so. Treatment-emergent adverse events claimed the lives of two individuals in each trial group. Despite the promising overall survival with nab-paclitaxel + gemcitabine, the primary endpoint was not reached.
Source: https://ascopubs.org/doi/10.1200/JCO.22.01134?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT01964430
Tempero M, Pelzer U, O’Reilly E, Winter J, Oh DY, Li CP, Tortora G, Chang HM, Lopez C, Bekaii-Saab T, Ko A, Santoro A, Park JO, Noel M, Frassineti G, Shan YS, Dean A, Riess H, Cutsem E, Berlin J, Philip P, Moore M, Goldstein D, Tabernero J, Li M, Ferrara S, Bruchec Y, Zhang G, Lu B, Biankin A, Reni M; APACT Investigators. Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 15:JCO2201134. doi: 10.1200/JCO.22.01134. Epub ahead of print. PMID: 36521097.
