Nab-Paclitaxel Plus Gemcitabine Misses DFS Endpoint in Pancreatic Cancer

The adjuvant combination of nab-paclitaxel (Abraxane) and gemcitabine was not found to improve disease-free survival (DFS) compared with gemcitabine alone, as confirmed by independent radiological review, in patients with pancreatic cancer, according to topline findings of the phase III APACT trial (NCT01964430).¹

However, there was an improvement in overall survival (OS) with the combination versus gemcitabine alone, reaching nominal statistical significance. The safety profile observed was consistent with prior reported studies of nab-paclitaxel. Full findings will be presented at an upcoming medical meeting, stated Celgene, the manufacturer of nab-paclitaxel, in a press release.

In the international, multicenter, open-labelled, controlled, phase III APACT study, 866 patients with surgically resected pancreatic adenocarcinoma were randomized to receive nab-paclitaxel plus gemcitabine compared with gemcitabine alone. Nab-paclitaxel was administered intravenously (IV) at 125 mg/m² on days 1, 8, and 15 of a 28-day cycle and IV gemcitabine at 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle for a total 6 cycles. In the gemcitabine alone arm, the agent was given IV at 1000 mg/m² on days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles.

To be eligible for enrollment, patients had to have histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection; pancreatic cancer surgical staging of T 1-3, N0-1, M0 disease; was able to start treatment no later than 12 weeks following surgery; was ≥18 years of age at the time of signing an informed consent form; had an ECOG performance status of 0 or 1; had acceptable hematology parameters; had acceptable blood chemistry levels; had CA19-9 <100 U/mL assessed within 14 days of randomization; and had acceptable coagulation studies.

Those who received prior neoadjuvant treatment or radiation therapy, had metastatic disease, had any other malignancy within 5 years of randomization, had an active infection requiring systemic therapy, and/or had known hepatitis B or C infection or HIV infection were excluded.

The primary endpoint was DFS; secondary endpoints included OS and number of patients with adverse events.

Previously, in patients with newly diagnosed locally advanced pancreatic cancer, induction therapy with nab-paclitaxel combined with gemcitabine led to an 8.8-month time to treatment failure (90% CI, 6.67-9.82), according to updated single-arm findings from the phase II LAPACT trial that were presented at the 2018 Gastrointestinal Cancers Symposium.²

In the international study, 106 patients at a median age of 65 years with locally advanced pancreatic cancer were enrolled. Induction therapy was administered with nab-paclitaxel at 125 mg/m² plus gemcitabine at 1000 mg/m² on days 1, 8, and 15 of a 28-day cycle for 6 total cycles. All patients had not received prior therapy for pancreatic cancer and were classified as unresectable. Following the induction phase, patients were offered continuation of nab-paclitaxel/gemcitabine or a switch to another type of therapy.

Additional results showed that nab-paclitaxel/gemcitabine led to a 32% objective response rate and an overall DCR of 77.6%. All responses in the study were partial responses. Additionally, the median progression-free survival was 10.8 months (90% CI, 9.26-11.63) with the combination and the 12-month OS rate was 72% (90% CI, 64.5%-78.9%).

Moreover, the stable disease rate for ≥16 weeks was 44.9% and 32.7% of patients had stable disease for ≥24 weeks. The ≥16 week DCR was 77.6% and the ≥24 week DCR was 65.4%.

Celgene added in the press release that there are currently more than 130 studies evaluating nab-paclitaxel in patients with pancreatic cancer in combination with more than 50 novel agents.

References

1. Celgene Provides Update on ABRAXANE Combination Therapy in the Treatment of Metastatic Triple-Negative Breast Cancer and Pancreatic Cancer. Celgene. Published March 12, 2019. https://bit.ly/2HmHy2X. Accessed March 12, 2019.
2. Hammel P, Lacy J, Portales F, et al. Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC). J Clin Oncol. 2018;36 (suppl 4S; abstr 204). doi: 10.1200/JCO.2018.36.4_suppl.204