Antacids linked to reduced erlotinib efficacy

By Laura Cowen, medwireNews Reporter

Acid suppression (AS) therapy may negatively impact outcome among patients receiving erlotinib for advanced non-small-cell lung cancer (NSCLC), Canadian study findings show.

The researchers therefore advise “caution” to oncologists prescribing tyrosine kinase inhibitors (TKIs) such as erlotinib to patients who are already receiving AS, as well as to general practitioners “who may inadvertently prescribe acid suppressants outside of a patient’s cancer care.”

The team, led by Michael Sawyer from the University of Alberta in Edmonton, explains that TKIs often have pH-dependent solubility, with erlotinib reaching maximal solubility in solutions with a pH of 2. Since proton pump inhibitors (PPIs) – the most commonly used acid suppressants – yield a median gastric pH of more than 5, it is likely that “erlotinib would have substantially reduced ability to dissolve” in patients concurrently using PPIs.

To investigate whether this affects clinical outcome, Sawyer and colleaguesreviewed data for 507 advanced (stage IIIB or IV) NSCLC patients (median age 64 years, 54% women) receiving erlotinib from 2007 to 2012 at a large, centralised cancer institution in Canada.

A quarter (n=124) of these patients received concomitant AS, most commonly with a PPI (93%), and the researchers note that there were no statistically significant differences in NSCLC baseline characteristics or Charlson comorbidity index between the AS and non-AS groups.

As reported in Clinical Lung Cancer, patients in the AS group had significantly shorter median progression-free survival (PFS) and overall survival (OS) compared with those in the non-AS group, at 1.4 versus 2.3 months and 12.9 versus 16.8 months, respectively.

After accounting for gender, NSCLC subtype and performance status, patients receiving AS had a significant 1.83-fold increased risk of disease progression and a 1.37-fold increased risk of death compared with those who did not receive AS.

The researchers also found that AS therapy was associated with a significantly worse objective response rate (5.6 vs 18.5%), as well as lower rates of erlotinib treatment-limiting toxicity (0.8 vs 7.0%) and TKI-related rash (47.6 vs 63.2%).

Sawyer et al comment that they could not determine whether there is a threshold for the amount of concomitant AS therapy that may impact erlotinib because the majority (81%) of AS-therapy patients received 100% prescription overlap with erlotinib.

They conclude: “[G]iven the large focus of the oncologic world on oral targeted therapies, effects of gastric acidity on drug absorption may have implications for current and future oral anti-cancer therapies. Studies are warranted to determine if this effect applies to other TKIs.”

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