PPI, H2RA Use With Pazopanib Does Not Affect PFS, OS in Renal Cell Carcinoma

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Previous studies found that an elevated pH environment leads to nearly a 40% reduction in pazopanib exposure.
Previous studies found that an elevated pH environment leads to nearly a 40% reduction in pazopanib exposure.

Administering proton-pump inhibitors (PPI) or histamine type-2 receptor antagonists (H2RAs) with pazopanib does not negatively affect outcomes among patients with metastatic renal cell carcinoma (mRCC), according to a study published in The Oncologist.1

Patients with mRCC frequently experience dyspepsia or gastroesophageal reflux disease (GERD) and consequently receive PPIs or H2RAs. Previous studies found, however, that an elevated pH environment leads to nearly a 40% reduction in pazopanib exposure.

For this retrospective study, researchers evaluated the outcomes of 90 patients with mRCC who took pazopanib alone or concurrently with a PPI/H2RA. The majority of study patients were men, had a median age of 60 to 65 years, an ECOG performance status of 1, and had received 0 to 2 prior systemic therapies.

Patients who took a PPI/H2RA had a median progression-free survival (PFS) of 9.0 months (95% CI, 8.0-13.0) compared with 11.0 months (95% CI, 6.0-16.0) among patients who took pazopanib alone (hazard ratio [HR], 1.25; 95% CI, 0.76-2.07; P = .85).

The median overall survival (OS) was 28.0 months (95% CI, 19.0-41.0) vs 30.1 months (95% CI, 17.0-47.0) among patients who took concomitant PPIs/H2RAs vs pazopanib alone, respectively (HR, 0.99; 95% CI, 0.51-1.93; P = .92).

The only adverse event that occurred at a significantly different rate was dyspepsia/GERD: 33% of patients in the pazopanib alone arm reported dyspepsia/GERD compared with 4% among patients who received a PPI/H2RA (P = .005).

There were no significant differences in PFS or OS associated with PPI vs H2RA use.

The authors concluded that “based on the results of this retrospective cohort study and the nature of the treatment of patients with mRCC, clinicians should consider allowing patients to remain on concomitant pazopanib and acid-reducing therapy for symptomatic control of dyspepsia, GERD, or any other clinically appropriate indication.”

Reference

  1. McAlister RK, Aston J, Pollack M, Du L, Koyamab T, Chism DD. Effect of concomitant pH-elevating medications with pazopanib on progression-free survival and overall survival in patients with metastatic renal cell carcinoma. Oncologist. 2018 Feb 27. doi: 10.1634/theoncologist.2017-0578 [Epub ahead of print]

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