Nab-Paclitaxel Plus Gemcitabine Opens Up Treatment Options in Pancreatic Cancer


The combination of nab-paclitaxel (Abraxane) and gemcitabine is steadily gaining in popularity among oncologists in the treatment armamentarium for pancreatic adenocarcinoma, according to Fadi Braiteh, MD.

The combination is slowly being pushed toward the neoadjuvant and adjuvant settings in the disease type, though not without pushback from payers, said Braiteh, medical oncologist, director of the Translational Oncology Program (TOP)-Phase I and GI Malignancies Program, Comprehensive Cancer Centers of Nevada.

The FDA approved the nab-paclitaxel plus gemcitabine in September 2013 based on findings from the phase III MPACT trial, which compared the combination with gemcitabine alone. Median overall survival with nab-paclitaxel plus gemcitabine was 8.5 months compared with 6.7 months for gemcitabine alone (HR, 0.72;P<.001). In an extended follow-up, 4% of patients survived at least 36 months and 3% of patients survived at least 42 months.

TARGETED ONCOLOGY:Can you discuss the comparative effectiveness and resource utilization of nab-paclitaxel/gemcitabine versus FOLFIRINOX?


There are no data from any randomized, controlled trials comparing both regimens. Comparing the results across both trials is typically unacceptable, because of major differences in methodology, variation in study design, patient population, inclusion criteria, assessment type, and many others.

Whichever treatment clinicians and patients&rsquo; have the most comfort with is the regimen most often utilized. National guidelines have otherwise been equidistant from either regimen, when it comes to a recommendation. FOLFIRINOX utilization in practice is far from being homogenous, since providers have approved a variety of modified versions, omitting complements, and often adding growth factors.

After disease progression on a certain regimen in first-line, we saw oncologists utilizing a version of the other regimen in second-line—with significant modifications&mdash;although both were studied only as frontline therapy, mainly because of the lack of meaningful data supporting a second-line regimen.

TARGETED ONCOLOGY:Do you see nab-paclitaxel in addition to gemcitabine moving into earlier settings, such neoadjuvant or adjuvant?


Although ongoing trials did not mature with such results, this treatment combination is being largely adopted in practice, though not without some pushback from payers, unfortunately. The hypothesis is very optimistic and remains to be demonstrated. In solid tumors, there are numerous cases of a combination being efficacious in advanced cancers and failing in the adjuvant setting.

TARGETED ONCOLOGY:Has an optimal sequence of therapies emerged yet for pancreatic cancer?


The FDA approval of liposomal irinotecan plus 5-FU infusion post-gemcitabine based treatment (NAPOLI trial) could sway oncologists to use a gemcitabine/Abraxane combination in the front-line, when patient&rsquo;s performance status allows for a multidrug regimen. Physicians tend to use clinical parameters otherwise to triage patients for a gemcitabine doublet versus a triple drug treatment. There are clinical observations that some patients benefit from one regimen rather than the other regardless of the sequence, although there is no upfront predictor of how to sequence them.

TARGETED ONCOLOGY:What makes second-line treatment in pancreatic cancer so difficult?


A good proportion of patients, close to 50% in certain instances, have such an aggressive biology with rapid clinical deterioration that makes them less suitable for an aggressive treatment, even less for a clinical trial.

TARGETED ONCOLOGY:Could nab-paclitaxel help open the door toward more efficacious second-line treatments?


Yes, and data shows in real practice that is the case, although there is a bias to utilization of frontline FOLFIRINOX to the most fit patients in the frontline, hence an imbalance with sicker patients getting either gemcitabine alone or combined with Abraxane.

TARGETED ONCOLOGY:There are a number of nab-paclitaxel/gemcitabine combinations now being explored. Can you discuss what makes these agents ideal for combinations?


With the failure of the evofosfamide plus gemcitabine trial to demonstrate superiority, it has left us with gemcitabine plus Abraxane as the preferred comparator standard of care, at least from an FDA perspective. Any investigative agents, such as PEGPH20, are added to that doublet backbone in frontline randomized controlled trials.

TARGETED ONCOLOGY:Where do you hope to see the treatment paradigm of pancreatic cancer going in the future?


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