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Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Research

Background:

  • Immunotherapy, particularly with pembrolizumab, has revolutionized advanced non-small-cell lung cancer (NSCLC) treatment.
  • However, the impact of concomitant medications on immunotherapy efficacy remains a critical area of investigation.
  • Antibiotics, steroids, and proton pump inhibitors (PPIs) are frequently used in cancer patients and are suspected to interfere with immune checkpoint inhibitors.

Purpose of the Study:

  • To investigate the association between comedications (antibiotics, steroids, PPIs) and overall survival (OS) in patients with advanced NSCLC receiving first-line pembrolizumab.
  • To determine if specific classes or dosages of these comedications influence treatment outcomes.

Main Methods:

  • A nationwide retrospective cohort study using French national health care data from January 2015 to December 2022.
  • Target trial emulation included patients with advanced NSCLC treated with first-line pembrolizumab, alive at 2 months post-initiation.
  • Inverse probability of treatment weighting (IPTW) was used to adjust for confounding factors between exposed and unexposed groups.

Main Results:

  • Antibiotic exposure (excluding macrolides and penicillins) was associated with shorter OS (HR, 1.08).
  • Steroid use showed no significant association with OS overall (HR, 0.98), but a dose-dependent negative impact was observed at higher doses (>20 mg prednisone equivalent for pembrolizumab alone, >30 mg for pembrolizumab plus chemotherapy).
  • Proton pump inhibitor (PPI) exposure was significantly associated with worse OS (HR, 1.13).

Conclusions:

  • Comedication with certain antibiotics, high-dose steroids, and PPIs is associated with worse overall survival in advanced NSCLC patients treated with pembrolizumab.
  • These findings underscore the importance of careful consideration and monitoring of comedications in patients undergoing immunotherapy.
  • Further research into the mechanisms of interaction and optimal management strategies for these comedications is warranted.