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Gastric Acid Suppressants May Reduce Survival Outcomes in Patients With Sarcoma Treated With Pazopanib

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Key Points

  • Patients with soft-tissue sarcoma who concomitantly used a gastric acid suppressant during pazopanib treatment had significantly reduced progression-free survival compared to nonusers: 2.8 months vs 4.6 months, respectively; and reduced overall survival: 8.0 months vs 12.6 months, respectively.
  • Therapeutic drug monitoring of pazopanib plasma concentrations may be helpful for patients on pazopanib and gastric acid suppressant therapy.

It is estimated that 20% to 33% of patients undergoing cancer treatment are concomitantly using a gastric acid suppressant, most commonly a proton pump inhibitor (including omeprazole and esomeprazole magnesium) or a histamine H2-receptor blocker (such as ranitidine). A study by Mir et al investigating whether gastric acid suppressive agents negatively impact the effectiveness of pazopanib in patients with soft-tissue sarcoma has found that the long-term use of gastric acid suppressive therapy with pazopanib was associated with significantly shortened progression-free survival and overall survival.

Complete withdrawal of gastric acid suppressive agents must be considered whenever possible in these patients, the researchers concluded. The report was published in Clinical Cancer Research.

Methodology and Results

The researchers analyzed data from the completed EORTC phase II 62043 and phase III 62072 clinical trials of patients with advanced soft-tissue sarcoma treated with pazopanib. The researchers first compared the outcome of patients treated with pazopanib with or without gastric acid suppressive agents for ≥ 80% of treatment duration, and subsequently using various thresholds. Of the 333 eligible patients evaluated, 59 (17.7%) received concomitant gastric acid suppressive therapy for > 80% of pazopanib treatment duration. 

The impact of concomitant gastric acid suppressive therapy was assessed on progression-free survival and overall survival using multivariate Cox models, exploring and comparing the potential effect on placebo-treated patients. Median progression-free survival was shorter in gastric acid suppressive therapy users vs nonusers: 2.8 months vs 4.6 months, respectively (hazard ratio [HR] = 1.49; 95% confidence interval [CI] = 1.11–1.99; P = .01). Concomitant administration of gastric acid suppressive therapy was also associated with a shorter median overall survival: 8.0 months vs 12.6 months (HR = 1.81: 95% CI = 1.31–2.49; P < .01).

The longer the overlapping use of gastric acid suppressive agents and pazopanib, the worse the outcome with pazopanib, according to the study results. These results were not observed in placebo-treated patients (HR = 0.82; 95% CI = 0.51–1.34; P = .43 for progression-free survival; and HR = 0.84; 95% CI = 0.48–1.48; P = .54 for overall survival).

“Coadministration of long-term gastric acid suppressive therapy with pazopanib was associated with significantly shortened [progression-free and overall survival]. Withdrawal of gastric acid suppressive agents must be considered whenever possible. Therapeutic drug monitoring of pazopanib plasma concentrations may be helpful for patients on pazopanib and gastric acid suppressive therapy,” concluded the study authors.

Clinical Relevance

“Our results indicate that gastric acid suppressants reduce the efficacy of pazopanib in patients with advanced soft-tissue sarcoma,” said Olivier Mir, MD, PhD, MPH, a medical oncologist and clinical pharmacologist at the Gustave Roussy Cancer Institute, University of Paris-Sud, and lead author of this study, in a statement. “Oncologists and pharmacists should pay close attention to patients’ concurrent medications, as they may have a significant impact on cancer treatment outcomes. 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.”

Dr. Mir is the corresponding author of this study.

Disclosure: Funding for this study was provided by Fonds Cancer from Belgium. The study authors' full disclosures can be found at clincancerres.aacrjournals.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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