Induction Regimen Achieves 80% DCR in Advanced Pancreatic Cancer

Jill Lacy, MD

A novel chemotherapy combination led to a disease control rate of 80% in a small study of patients with locally advanced pancreatic cancer.

The combination of nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) and gemcitabine led to no new or unexpected adverse events. Grade 3/4 neutropenia occurred in almost half of the 47 patients in the phase II MPACT trial. Otherwise, grade 3/4 adverse events (AEs) were relatively uncommon.

“The 80% disease control rate for the first 47 patients to complete the nab-paclitaxel plus gemcitabine induction phase is promising and indicative of antitumor activity in patients with locally advanced pancreatic cancer,” Jill Lacy, MD, a medical oncologist at the Yale Cancer Center in New Haven, Connecticut, and colleagues reported at the Gastrointestinal Cancers Symposium in San Francisco. “Notably, all patients were identified as unresectable at baseline; yet, 13% were resectable after the nab-paclitaxel plus gemcitabine induction phase.”

Most patient-reported symptoms stabilized or improved during induction therapy, they added.

Patients with locally advanced pancreatic cancer have few treatment options and a poor prognosis comparable to that of metastatic disease. In a phase III MPACT trial of patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine led to almost a threefold increase in the magnitude of reduction in primary tumor size as compared with gemcitabine alone.¹

On the basis of the phase III MPACT trial results, a phase II LAPACT trial of nab-paclitaxel and gemcitabine in locally advanced pancreatic cancer was initiated. Enrollment was limited to patients with previously untreated disease that was judged to be unresectable. Patients with borderline-resectable disease were excluded.

All patients received induction with nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m², both administered weekly for 3 out of every 4 weeks for a maximum of 6 cycles of therapy. Treatment choices beyond induction were at investigators discretion.

The trial had a primary endpoint of time to treatment failure. Secondary objectives included disease control rate, overall response rate, progression-free survival, overall survival, and quality of life.

The study population had a median age of 65, ECOG performance status 0/1, and slight female predominance (27 of 47). The median value of the sum of the longest diameters of target lesions was 43 mm. Lacy and colleagues reported that 28 patients completed the induction phase. Overall, the patients received a median of 5 cycles of induction therapy.

Following induction, 25 patients received additional treatment: 5 received additional nab-paclitaxel and gemcitabine, 10 received chemoradiation, and 10 underwent surgery.

Commonly occurring AEs (all grades) included neutropenia (66% all grade, 45% grade 3/4), anemia (49%, 13%), and fatigue (45%, 11%). Other relevant AEs were diarrhea (47%, 2%), thrombocytopenia (28%, 2%), peripheral neuropathy (15%, 2%), and febrile neutropenia (2% all grade and grade 3/4).

All but 2 of the patients were evaluable for efficacy. Best response during induction included partial response in 14 patients and stable disease for 16 weeks or longer in 22 patients resulting in the disease control rate of 80% (36 of 45). An additional 6 patients had briefer intervals of stable disease.

Although all patients were considered to have unresectable disease at enrollment, 6 patients (13%) has post-induction surgery. One of the patients had R0 surgical results (clear margins), 4 had R1 resections, and 1 had an R2 resection.

Quality-of-life data for 36 patients showed clinically meaningful improvement in disease-related symptoms in the vast majority of patients. Patient ratings for more than 2 dozen symptoms showed that weakness improved in 67%. For all other rated symptoms, the proportion of patients with improvement ranged from 75% to 94%.

References

1. Kunzmann V, Ramanathan RK, Goldstein D, et al. Tumor reduction in primary and metastatic pancreatic cancer lesions with nab-paclitaxel and gemcitabine: an exploratory analysis from a phase 3 study. Pancreas. 2017;46(2):203-208. doi: 10.1097/MPA.0000000000000742.
2. Lacy J, Portales F, Hammel P, et al. Interim results of a multicenter phase II trial of nab-paclitaxel plus gemcitabine for patients with locally advanced pancreatic cancer. Poster presented at: 2017 Gastrointestinal Cancers Symposium; January 19-21, 2017; San Francisco, CA. Abstract 358.