ATLANTA – With more cancer patients using immune checkpoint inhibitors, drug-drug interactions are of increasing interest. Researchers are finding that some concomitant medications appear to affect outcomes from immunotherapy.

Studies released as part of the 2021 American Society of Clinical Oncology (ASCO) annual meeting discussed two drug classes that show promise for enhancing the effect of ICIs.

In one study, Emory University and Atlanta VA Healthcare System researchers discussed the benefits of concomitant nonsteroidal anti-inflammatory (NSAID) medications with immunotherapy. Their retrospective cohort study used the VA Corporate Data Warehouse (VA-CDW) to identify patients diagnosed with NSCLC who were treated with ICIs between 2010-18 and to determine who received NSAID prescriptions from VA pharmacies within 90 days of the first ICI infusion.1

The study cohort included 3,415 patients with NSCLC treated with ICIs, with 64% of them having received concomitant NSAIDs. Participants’ median age was 69; most, 97%, were male; 73% were white and 21% Black, and the majority, 66%, lived in urban areas.

Initial diagnosis for most of the patients was stage III or IV disease (68%); tumor histology: adenocarcinoma 48% and squamous cell 38%. While 40% had no reported comorbidities, 30% had one to three and 30% had four or more. Slightly more than half, 54%, of the NSCLC patients had received chemotherapy before ICI, and another 31% received the two therapies concurrently.

In terms of NSAIDs, the most commonly used ones were aspirin (35%), ketorolac (11%), and ibuprofen (7%), with 44% of participants exposed to more than one NSAID.

With a median follow-up of eight months, results indicated that exposure to concomitant NSAIDs was associated with longer overall survival (HR = 0.90; 0.83-0.98, p = 0.01) after adjusting for all available potential confounders on multivariable analyses. Researchers explained that longer OS persisted following propensity score matching (HR = 0.89; 0.82-0.97 p = 0.007).

The authors pointed to other factors that also appeared significant for overall survival, including:

  • use of chemotherapy after ICI (HR = 0.53 [0.40-0.69], p < 0.001),
  • concurrent chemotherapy during ICI (HR = 0.68 [0.62-0.74], p < 0.001),
  • younger age,
  • Black race,
  • female gender, and
  • adenocarcinoma histology.

Only diclofenac approached statistical significance (HR = 0.78 [0.59-1.03], p = 0.08), among the NSAIDs analyzed. “This retrospective cohort study of veterans with NSCLC who were treated with ICI identified that concomitant receipt of NSAIDs is associated with longer OS,” the authors wrote.

Some of the same researchers from Emory and the Atlanta VA also looked at certain azole derivatives as having antitumor efficacy and the benefit of modulated responses to ICIs, explaining, “Clinical evidence of synergy can support ongoing research that is investigating the role of repurposing current FDA-approved azole medications to improve outcomes in people with non-small cell lung cancer (NSCLC).”2

Focusing on veterans diagnosed with NSCLC between 2010-2018 who were treated with ICI, the study team defined receipt of azole drugs as taking a systemic azole within 90 days of ICI therapy. Of the 3,413 veterans treated with ICI, 9.5% were treated with an azole, most commonly clotrimazole (3.0%) and fluconazole (2.5%), according to the report.

Those patients predominantly had stage IV disease (40.8%) at initial diagnosis, followed by stage III (27.1%), stage I-II (19.9%), and unknown stage (12.1%). While propensity score-matched analysis with 324 patients in each cohort did not document a significant difference in overall survival (HR = 0.89 [0.75-1.06]; p = 0.18) between patients who received any azole vs. those who did not, associations with longer overall survival were identified with use of clotrimazole (HR = 0.72 [0.56 – 0.92]; p = 0.009) and with taking more than one azole (HR = 0.71 [0.53-0.96]; p = 0.026) when compared with no azoles.

On the other hand, no such link was documented for miconazole (HR = 1.92 [1.30-2.832]; p = 0.001), itraconazole (p = 0.08), fluconazole (p = 0.20), or ketoconazole (p = 0.87).

“In the matched analysis of 102 clotrimazole patients versus no azole, OS was longer in patients who received clotrimazole (HR = 0.76; 95% CI 0.55 – 1.04; p = 0.087), although this effect was not statistically significant,” researchers reported. “This analysis demonstrated a trend towards longer survival with concomitant clotrimazole and ICI for advanced NSCLC. This association was not seen for other azole mediations.”

 

  1. Moghanaki D, Stokes WA, Behera M, Jiang R. (June 4-8, 2021). Association of concomitant NSAID and immunotherapy on outcomes in patients with non-small cell lung cancer: Analysis of the National Veterans Health Administration Database.ASCO 2021 annual meeting. Virtual. https://meetinglibrary.asco.org/record/200666/abstract
  2. Sebastian N, Stokes WA, Behera M, Jian R. (June 4-8, 2021). Association of azole antifungals with survival in patients with non-small cell lung cancer receiving immunotherapy. ASCO 2021 annual meeting. Virtual. https://meetinglibrary.asco.org/record/199431/abstract