Ruxolitinib plus capecitabine extended survival in metastatic pancreatic cancer

CHICAGO — The addition of ruxolitinib to capecitabine extended OS and PFS in patients with metastatic pancreatic cancer who had elevations in blood levels of C-reactive protein, according to results of a phase 2 study presented at the 2014 ASCO Annual Meeting.

The combination also yielded significant improvements in patients response rate, clinical benefit and weight gain, according to Herbert Hurwitz, MD, professor of medical oncology at Duke University School of Medicine, and colleagues.

The analysis included 127 patients whose disease progressed after treatment with gemcitabine (Gemzar, Eli Lilly).

All patients received 1,000 mg/m² capecitabine (Xeloda, Hoffmann-La Roche) twice daily on days 1 through 14 of a 21-day cycle. Researchers randomly assigned 64 patients to receive twice-daily 15-mg doses of the JAK1/JAK2 inhibitor ruxolitinib (Jakafi, Incyte), and the other 63 patients received placebo.

In unselected patients, researchers observed a trend toward improved OS (HR=0.79; 95% CI, 0.53-1.18) and PFS (HR=0.75; 95% CI, 0.52-1.10) in the ruxolitinib arm. The confirmed overall response rate was 7.8% in the ruxolitinib arm vs. 0% in the placebo arm.

Researchers then evaluated a subgroup of 60 patients with local and systemic inflammation, defined as serum C-reactive protein levels greater than the group median of 13 mg/L.

In this analysis, researchers observed significantly improved OS (HR=0.47; 95% CI, 0.26-0.85) and a trend toward improved PFS (HR=0.62; 95% CI, 0.35-1.1) favoring those patients assigned ruxolitinib.

Patients with serum C-reactive protein ≤13 mg/L who received ruxolitinib also demonstrated improvements in OS (HR=0.89) and PFS (HR=0.82), but the differences between arms were not significant.

The subgroup analysis showed that 3-month survival (48% vs. 29%) and 6-month survival (42% vs. 11%) were higher among patients assigned to ruxolitinib.

Researchers also evaluated outcomes based on patients’ modified Glasgow Prognostic Score (mGPS), which measures systemic inflammation. Patients with a mGPS score of 2 demonstrated significantly improved OS with ruxolitinib (HR=0.49). Researchers observed slight improvements among patients with a score of 1 (HR=.71), but little benefit among patients with a score of 0 (HR=0.91).

Overall, a majority of patients in both arms experienced a grade 3 or grade 4 adverse event (ruxolitinib, 75%; placebo, 82%). More patients assigned ruxolitinib experienced grade 3 or grade 4 anemia (15.3% vs. 1.7%). Grade 3 or grade 4 neutropenia and thrombocytopenia occurred in 1.7% of patients assigned ruxolitinib and no patients assigned placebo.

For more information:

Hurwitz H. Abstract #4000. Presented at: 2014 ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The researchers report consultant/advisory roles with, employment/leadership positions with, research funding from and stock ownership in Bristol-Myers Squibb, Genentech, Incyte, Novartis, Pfizer, Roche and Sanofi.