Hicks, J Kevin

Abstract Introduction The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer‐related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6 ‐guided opioid prescribing for patients with cancer and reported pilot outcome data. Methods Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation‐effectiveness clinical trial and randomized to CYP2D6 ‐genotype‐guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient‐reported pain and symptom scores at baseline and up to 8 weeks, were assessed. Results Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3–37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6 ‐genotype‐guided recommendations to change therapy ( n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow‐up questionnaires ( n = 48), there was no difference in change in mean composite pain score (−1.01 ± 2.1 vs. −0.41 ± 2.5; p = 0.19) or symptom severity at last follow‐up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm ( n = 26) and genotype‐guided arm ( n = 22), respectively. Conclusion Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype‐guided recommendations was low, impacting assessment of pain‐related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.

The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations.