Feasibility of preemptive pharmacogenetic testing in colorectal cancer patients within a community oncology setting.

INTRODUCTION: Pharmacogenetics, in hand with precision medicine in oncology, represents an opportunity to holistically tailor a patient's treatment regimen using both somatic and germline variants to improve efficacy and decrease toxicity. Colorectal cancer patients represent a population with frequent use of fluoropyrimidine and irinotecan and are an ideal opportunity for implementation of preemptive pharmacogenetics as evidence supports pharmacogenetic testing for DPYD and UGT1A1 to reduce fluoropyrimidine and irinotecan toxicities. METHODS: This was a single arm proof-of-concept study at a large community-based health system. Participants provided samples for pharmacogenetic testing via an external vendor prior to chemotherapy initiation and an oncology pharmacist was responsible for pharmacogenetic interpretation and pharmacogenetic-guided therapeutic recommendation to the treating provider. RESULTS: A total of 24 (60%) participants had a UGT1A1 variant. All participants (100%) were DPYD*1/*1. Results were available and interpreted for 29/40 (72.5%) participants prior to scheduled chemotherapy initiation (p value <0.014). Of the participants whose results were available in 5 weekdays or less (n = 23), 20 (87%) were communicated with the treating provider prior to scheduled chemotherapy administration. A total turnaround time of 5 days or less was significantly associated with PGx feasibility in a community-based oncology clinic (p = 0.03). CONCLUSIONS: In conclusion, we were able to show that implementation of preemptive pharmacogenetic testing into a community oncology clinic with results interpretation available prior to scheduled initiation of chemotherapy was feasible. As pharmacogenetic testing in oncology expands, pharmacists should be prepared to optimize supportive medication regimens as well as chemotherapy with pharmacogenetic results.

Successful alectinib desensitization in a patient with anaplastic lymphoma kinase-positive adenocarcinoma of the lung and alectinib-induced drug rash.

INTRODUCTION: Alectinib is an oral tyrosine kinase inhibitor currently recommended by the National Comprehensive Cancer Network (NCCN) as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase (ALK) gene rearrangement-positive non-small cell lung cancer (NSCLC). Skin toxicity is a known adverse effect of this medication, yet current recommendations are unclear regarding how to best manage patients who develop severe skin toxicity while taking alectinib. CASE REPORT: Here, we describe a case of successful rechallenge with alectinib by utilizing a desensitization procedure in a patient who had developed severe alectinib-induced skin toxicity about two weeks into treatment.Management and outcome: Upon resolution of the initial skin toxicity symptoms, the patient was rechallenged with alectinib using a modified version of a previously published desensitization procedure. The patient tolerated the rechallenge with no recurrence of skin toxicity or other adverse effects and was able to continue treatment with alectinib. DISCUSSION: Alectinib is currently recommended as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase gene rearrangement-positive NSCLC due to improved progression-free survival when compared to crizotinib. The development of skin toxicity can lead to early discontinuation of alectinib treatment, forcing providers and patients to select alternative, potentially less effective options. This case report provides evidence that patients who have experienced severe skin toxicity due to alectinib may be able to continue this first-line treatment option by rechallenging them using a desensitization procedure.