A retrospective analysis published in the Journal of Experimental Medicine showed that patients with PIK3CA-altered head and neck cancer had improved survival outcomes if they regularly took nonsteroidal anti-inflammatory drugs (NSAIDs).1 Although the findings must be validated in a prospective clinical trial, the study highlights how old drugs, like aspirin, can be repurposed as personalized treatments for patients with a specific genomic aberration.
“This is a potential example where unrecognized benefits may be right under our nose,” study coauthor Robert Ferris, MD, PhD, told Cancer Therapy Advisor. Dr Ferris is the director of UPMC Hillman Cancer Center, Pittsburgh, PA. “We have to have a broader view of the activity of some of these drugs.”
Krzysztof Misiukiewicz, MD, head and neck oncologist at Mount Sinai, New York, New York, was not involved in the study, but expressed a similar sentiment during an interview with Cancer Therapy Advisor. “[Given] the high cost of the drugs that we currently have, repurposing old drugs, I think, is a good way to find other treatment options that are going to be cheaper, but at the same time efficacious.”
To determine whether NSAIDs confer a survival benefit, a cohort of 266 patients with head and neck squamous cell carcinoma (HNSCC) were retrospectively evaluated. PIK3CA status was determined for each patient, and 75 patients (28%) were found to have a PIK3CA mutation, amplification, or both in their tumor tissue.
Information about NSAID use was obtained from electronic medical records, and patients were labeled as regular users if they took NSAIDs at least 2 days per week for at least 6 months. Most patients who regularly used an NSAID (93%) took aspirin as part of an NSAID regimen; most of these regular users (86%) started taking NSAIDs at some point after being diagnosed with HNSCC. The decision to start taking NSAIDs was not the result of the diagnosis.
In a multivariate analysis that accounted for cancer type (primary vs recurrent), stage, and human papilloma virus (HPV) status, regular NSAID use was significantly associated with longer disease-specific survival (DSS) for patients with a PIK3CA aberration. For regular users, the 5-year DSS rate was significantly higher among PIK3CA-altered HNSCC patients compared with those without an aberration (72% vs 25%; P =.0032). PIK3CA-altered HNSCC patients who were regular users also had a 76% lower likelihood of dying from cancer during that time period (hazard ratio [HR]=0.24; 95% CI, 0.09–0.62).
In a multivariate analysis that accounted for PIK3CA status, cancer type, stage, HPV status, and age at surgery, regular NSAID use was associated with improved overall survival (OS) among patients with PIK3CA aberrations. For regular users, the 5-year OS rate was significantly higher for PIK3CA-altered HNSCC patients compared with those without an aberration (78% vs 45%; P =.0043). PIK3CA-altered HNSCC patients who were regular users also had a 69% lower likelihood of dying during that time period (HR=.31; 95% CI, 0.12-0.69).
“Regardless of the smoking status, HPV status, or any other kind of cofounders, if [patients] do have the [PIK3CA] mutation and they take the nonsteroidal medications on a regular basis, obviously their risk of dying from the cancer [and] overall mortality goes down,” concluded Dr Misiukiewicz.
Dr Ferris and his colleagues also proposed a possible mechanism by which NSAIDs confer antitumor benefits. On the basis of data from preclinical experiments, they proposed that PIK3CA aberrations turn on the PI3K pathway in tumors, which activates the cyclooxygenase-2 enzyme — the target of NSAIDs — and elevates prostaglandin E2 levels and ultimately, sensitizes the tumor to NSAIDs.
Even though NSAIDs have few side effects, Dr Ferris said, “We wouldn’t want to automatically tell everybody that we’ve solved the disease and start taking aspirin.” These retrospective findings need to be validated prospectively to change practice recommendations, he added.
- Hedberg ML, Peyser ND, Bauman JE, et al. Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. J Exp Med. 2019;216(2):419-427.