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Gastric acid suppressants reduce efficacy of pazopanib in sarcoma
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Concomitant administration of gastric acid-suppressant therapy with pazopanib significantly reduced PFS and OS in patients with soft tissue sarcoma, according to an analysis of data from phase 2 and phase 3 randomized trials published in Clinical Cancer Research.
“Our results indicate that gastric acid suppressants reduce the efficacy of pazopanib [Votrient, Novartis] in patients with advanced soft tissue sarcoma,” Olivier Mir, MD, MPH, medical oncologist and clinical pharmacologist at Gustave Roussy Cancer Institute in Paris, said in a press release. “Oncologists and pharmacists should pay close attention to patients’ concurrent medications, as they may have a significant impact on cancer treatment outcomes.”
Gastric acid-suppressive agents, including proton pump inhibitors and histamine H2-receptor blockers, are used in as many as half of patients receiving cancer treatment. However, the significance of the interactions these agents have with other drugs such as pazopanib — a pH-dependent multi-kinase inhibitor approved for treatment of advanced soft tissue sarcoma after prior chemotherapy — may be underestimated.
Mir and colleagues reviewed data on 333 patients with advanced soft tissue sarcoma treated with pazopanib in a phase 2 (n = 118) or a phase 3 (n = 215) trial evaluating the drug in this patient population.
More than one-third of the patients (n = 117) received gastric acid-suppressive therapy at least once during the pazopanib treatment period, 17.7% (n = 59) received it concomitantly during more than 80% of the pazopanib treatment period, and 5.7% (n = 19) had been using it at the time of trial registration.
Among the 110 patients who received placebo instead of pazopanib, 35 were treated with gastric acid-suppressive therapy.
PFS and OS served as primary and secondary endpoints.
Median follow-up from registration and randomization was 27.6 months (interquartile range, 22.9-35.4).
Results showed patients who received concomitant pazopanib and gastric acid-suppressive therapy had shorter median PFS (2.8 months vs. 4.6 months; HR = 1.49; 95% CI, 1.11-1.99) and OS (8 months vs. 12.6 months; HR = 1.81; 95% CI, 1.31-2.49) than patients who received pazopanib only.
Longer overlapping use of the therapies appeared associated with worse outcomes.
Patients who received placebo did not demonstrate these changes in PFS (HR = 0.82; 95% CI, 0.51-1.34) or OS (HR = 0.84; 95% CI, 0.48-1.48).
Researchers did not consider proton pump inhibitor type and dose, which in addition to the relatively small sample size, served as limitations to the study.
“I think that our results are practice-changing, and I would discourage oncologists against prescribing gastric acid suppressants when patients are treated with pazopanib, unless it is the only option for the patient,” Mir said. “Patients often utilize [gastric acid-suppressive] therapy for abdominal pain, which is not always related to stomach acidity. I would predict that the majority of patients taking [gastric acid-suppressive] drugs could utilize a different therapy to aid in their abdominal discomfort.” – by John DeRosier
Disclosures: Mir reports ownership interests at Amplitude Surgical and Transgene; speakers bureau honoraria from Eli Lilly, Pfizer Roche and Servier; and consultant/advisory roles with Amgen, Bayer, Bristol-Myers Squibb Eli-Lilly, Ipsen, Lundbeck, Merck, Novartis, Pfizer, Roche, Servier and Vifor Pharma. Please see the study for all other authors’ relevant financial interests.
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