Nab-paclitaxel Plus Gemcitabine a Strong Predictor of Survival in Metastatic Pancreatic Cancer

Josep Tabernero, MD, PhD

Treatment with weekly nab-paclitaxel plus gemcitabine remains a strong independent predictor of both overall survival (OS) and progression-free survival (PFS) in patients with metastatic pancreatic cancer compared with gemcitabine alone, even after correcting for all confounding prognostic variables, a new analysis of the MPACT study shows.

Josep Tabernero, MD, PhD, of Vall d’Hebron University Hospital, Barcelona, Spain, and multicenter colleagues found that after correcting for known prognostic factors in metastatic pancreatic cancer, treatment with weekly nab-paclitaxel plus gemcitabine improved OS by 28% and PFS by 34% relative to gemcitabine alone in predominantly stage IV metastatic pancreatic cancer patients who had received no prior treatment for metastatic disease (P <.0001 for both endpoints).

Tabernero reported these findings July 3, 2013 at the European Society of Medical Oncology 15th World Congress on Gastrointestinal Cancer in Barcelona.

“In order to understand what the real impact of the addition of nab-paclitaxel is, we needed to consider other well-known prognostic factors that are usually evaluated in pancreatic cancer,” Tabernero explained in an interview with OncLive.

“The data show that by introducing all these variables in our multistep model, the addition of nab-paclitaxel to gemcitabine continues to be the most important factor. So this is another statistical model to show that there is no bias related to other confounding factors and that the treatment effect is the most significant one.”

For the MPACT trial, 842 patients with metastatic pancreatic cancer were randomized to receive nab-paclitaxel, 125 mg/m² plus gemcitabine, 1000 mg/m² on days 1, 8, and 15 every 4 weeks (that is, every week for 3 weeks, with the 4th week off) or the same dose of gemcitabine alone weekly for 7 weeks followed by 1 week of rest, and then on days 1, 8, and 15 every 4 weeks from cycle 2 onwards. Patients were also stratified by region, presence of liver metastases, and Karnofsky performance status (KPS ≥70).

Factors Predictive of OS

HR

P value

Treatment (Nab-p + G vs G)

0.72

.0001

Region (Eastern Europe vs NA)

1.22

.0765

Age (<65 vs ≥65 years)

0.81

.0190

KPS (70-80 vs 90-100)

1.60

<.0001

Liver metastases (Yes vs No)

1.81

<.0001

G = gemcitabine; NA = North America

At 36 months, median OS in the intent-to-treat (ITT) population was 8.5 months in the combination arm compared with 6.7 months for the gemcitabine alone arm (P = .000015).

“KPS, presence of liver metastases, age, region, and number of metastatic sites were the most important predictors of survival,” Tabernero said.

On univariate analysis, the baseline for cancer antigen 19-9 (CA19-9), a tumor marker for pancreatic cancer, also significantly predicted OS in the overall cohort. However, after correction for an array of other prognostic factors on multivariate analysis, CA19-9 no longer emerged as significant predictor of OS.

Factors Predictive of PFS

HR

P value

Treatment (Nab-p + G vs G)

0.66

<.0001

Region (Australia vs NA)

1.25

.0928

Age (<65 vs ≥65)

0.83

.0519

KPS (70-80 vs 90-100)

1.56

<.0001

Liver metastases (Yes vs No)

1.79

.0002

G = gemcitabine; NA = North America

For the PFS analysis, MPACT investigators found that the region of Australia; being 65 years of age and older; a KPS of 70-80, and the presence of liver metastases were all significant predictors of worse PFS.

“The safety profile of this regimen is also acceptable and manageable compared to other regimens, so this study suggests that nab-paclitaxel plus gemcitabine should definitely be considered as one of the most important treatment options for this disease,” Dr. Tabernero concluded.

Taberner J, Von Hoff DD, Moore MJ, et al. Phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer: influence of prognostic factors of survival. Presented at: ESMO 15th World Congress on Gastrointestinal Cancer; July 3-6, 2013; Abstract 0-001.

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