Nab-paclitaxel plus gemcitabine in the adjuvant setting did not improve disease-free survival in patients with pancreatic cancer compared to gemcitabine alone, according to topline results from the phase III APACT trial that have been confirmed by independent radiological review.
Nab-paclitaxel (Abraxane) plus gemcitabine in the adjuvant setting did not improve disease-free survival (DFS) in patients with pancreatic cancer compared to gemcitabine alone, according to topline results from the phase III APACT trial (NCT01964430) that have been confirmed by independent radiological review.1
Although the primary endpoint was not met, the combination did show improvement in overall survival (OS) and achieved nominal statistical significance. The safety profile for this combination was consistent with prior reported studies of nab-paclitaxel. Celgene, the manufacturer of nab-paclitaxel, announced that full findings will be presented at an upcoming medical meeting.
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/m2on days 1, 8, and 15 of a 28-day cycle and IV gemcitabine at 1000 mg/m2on 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/m2on 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/m2plus gemcitabine at 1000 mg/m2on 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.