Arturo Loaiza-Bonilla, MD
A bevy of clinical trials exploring the use of nabpaclitaxel (Abraxane) in various combinations and treatment settings aim to uncover future strategies for treating patients with pancreatic adenocarcinoma, which remains one of the deadliest forms of cancer.
The FDA approved the combination of nab-paclitaxel and gemcitabine in September 2013, based on findings from the phase III MPACT trial, which compared the combination with gemcitabine alone. Long-term survival data from MPACT were published in early 2015, and showed a sustained overall survival (OS) advantage.1
The median OS with nab-paclitaxel plus gemcitabine was 8.5 months compared with 6.7 months for gemcitabine alone (HR, 0.72; P
<.001). In the extended follow-up, a group of patients survived longer than 24 months in the nab-paclitaxel plus gemcitabine treatment arm, including 4% of patients who survived at least 36 months and 3% of patients who survived at least 42 months.
This success has led some researchers to explore the combination in other settings, outside of the metastatic disease space. The combination is being explored as an adjuvant therapy in the phase III APACT study for patients with pancreatic adenocarcinoma and as either a neoadjuvant or adjuvant therapy in the NEONAX trial for patients with resectable pancreatic cancer.
Neoadjuvant Nab-Paclitaxel/Gemcitabine Shows Early Promise
In a small retrospective case study exploring nab-paclitaxel plus gemcitabine as neoadjuvant therapy for borderline resectable or unresectable locally advanced pancreatic adenocarcinoma, both the R0 resection rate and the response rate were each 20%. Findings from the study were presented at the 2016 Gastrointestinal Cancers Symposium.2
“The cases who do the best and are able to undergo a long-term strategy are those who are able to get through surgery,” said co-author of the study Arturo Loaiza-Bonilla, MD, assistant professor of clinical medicine at the University of Pennsylvania. “An R0 resection means that the cancer was cut out completely, with all the edges completely free from tumor. Those are the ones with prolonged survival, whereas in an R1 resection, the pathologist looks at the sample with a microscope, and sees cancer cells at the margin.”
The study looked at 20 patients at a median age of 69 years. The most common ECOG performance status was 1 (55%). A majority of the patients had borderline resectable disease (n = 14; 70%).
“An R1 resection is almost the same as having no surgery at all. The outcomes are equally bad,” explained Loaiza-Bonilla. “Surgery is not really an option for these patients at the moment, so we’re trying to use chemotherapy and radiation to shrink the tumor so the patient can go to surgery.”
Out of 6 patients who went on to receive surgery, 83% also had preoperative radiation and 67% had R0 resections. All patients with an R0 resection (n = 4) were initially defined as borderline resectable. Two patients with unresectable disease by imaging at presentation were able to undergo potentially curative surgery, although an R0 resection was not achieved. Median progression-free survival was 9.1 months (95% CI, 6.2-12.0).
“The good thing about this trial is that the patients are too frail for the three-medicine combination, FOLFIRINOX, but in using only two agents, we’re able to achieve almost the same results,” said Loaiza-Bonilla. “The data we have now indicate that at least about 20% of the patients have a conversion to an R0 resection, and the overall disease control rate is about 90%.”
The majority of patients in the study received 6 to 9 doses of nab-paclitaxel and gemcitabine. The partial response rate was 20% and the stable disease rate was 70%. In total, dose reductions were required for 64% of patients, a finding that will be applied to future studies. “We had one patient who was 90 years old, and two more who were over the age of 80, one of whom, an 81-year-old lady, had one of the best responses. She had almost a complete response to therapy without the requirement of any radiation, and did remarkably well for almost 2 years,” Loaiza-Bonilla added. “She had some breaks. There has been some data published that suggests you can give the combination every two weeks, and the patient can recover within those two weeks from the side effects.”