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Program Number: B186
Session Name: Poster Session

Concomitant use of opioids and statins is associated with improved immunotherapy response and survival in patients with recurrent/metastatic head and neck cancer

Elihu Igbinadolor; Tyler J Kristoff; Dong M Shin; Conor E Steuer; Nabil F Saba; Nicole C Schmitt; Emory University

Introduction: Anti-PD-1 immune checkpoint blockade (ICB) is now a common first-line treatment for patients with recurrent/metastatic head and neck cancer (HNC), but many patients fail to respond. There is a growing interest in the impact of concomitant medications on responses to ICB, with studies in other tumor types showing poor responses in patients taking opioid pain medications and modest improvements in response to ICB in patients taking statins for hyperlipidemia (e.g., Cortellini et al., JITC, 2020). Our previous preclinical and retrospective clinical data suggest that use of specific statin drugs is associated with increased responses to ICB in HNC, but the effects of opioids have not been extensively studied in this patient population.

Methods: This is a retrospective, observational study of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who received at least 3 doses of pembrolizumab or nivolumab at our institution. Patients were excluded if they received less than three doses, had insufficient data recorded, or also received cabozantinib on a clinical trial. We recorded clinicopathologic characteristics including stage and p16 status, combined positive score, body mass index, and concurrent use of chemotherapy, radiation, and other treatments. We also recorded whether patients were taking opioid pain medications upon initiation of ICB or later during ICB therapy. The daily morphine equivalent was also calculated for each patient. Response to ICB was determined by reviewing routine surveillance imaging. Chi squared test was used to compare response according to different factors, and log rank test was used to compare survival outcomes.

Results: A total of 158 patients met inclusion criteria; 102 were taking opioids, and 44 were taking statins. Prior data showed that statins are independently associated with response to ICB, with no significant effect of statins alone on survival. There was no difference in objective response rate (ORR) based on opioid use at the start of immunotherapy (p = 0.74). There was also no significant difference in progression-free survival (PFS; p = 0.135), though patients not taking opioids had superior overall survival (OS; median OS 20.67 months versus 13.5 months in opioid users, p = 0.0021). Interestingly, when we looked at use of statins and opioids together, use of both drugs was associated with improved ORR (odds ratio 2.8), and use of opioids without statins was associated with worse ORR (odds ratio 0.34), though these results did not quite reach statistical significance (p = 0.06). Patients taking both statins and opioids had superior PFS versus patients taking either drug class alone (p = 0.018), with a similar trend for OS that did not quite reach significance (p = 0.0842).

Conclusions: Although our single-institutional study may be underpowered to determine whether there is an independent effect of statin + opioid on clinical outcomes, our data suggest a complex relationship between statins and opioids in HNSCC patients treated with ICB. Larger, prospective clinical studies are needed to verify these results, and preclinical studies are needed to determine how opioids and statins impact T-cell function and other aspects of the tumor microenvironment.

 

 

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