Axitinib Demonstrates Survival Benefit in Heavily Pretreated Unresectable Recurrent, or Metastatic Head and Neck Cancer

Heavily pretreated patients with unresectable recurrent or metastatic head and neck squamous cancer experienced an improvement in survival following treatment with axitinib.

Heavily pretreated patients with unresectable recurrent or metastatic head and neck squamous cancer (HNSC) experienced an improvement in survival following treatment with axitinib (Inlyta), according to a study published in Cancer.1

The agent yielded a median overall survival (OS) of 9.8 months, as well as a 6-month OS rate of 70%, meeting the study's protocol-defined criteria for clinical efficacy. Investigators additionally reported a best overall survival rate of 42%.

“Although the number of patients was small, our study was able to look at what happened to those who received immunotherapy after axitinib and found these patients’ cancers responded extremely well—similar to what we’ve seen from other studies where people received the treatments simultaneously,” said Paul Swiecicki, MD, lead author of the study and an assistant professor and medical oncologist with Michigan Medicine, University of Michigan, in a press release.2 “This supports the idea that we may be able to combine the two approaches in a new way by giving them sequentially rather than at the same time, which should cut down on the severity of the side effects.”

Currently, metastatic HNSC is considered a poor prognosis, incurable disease and has not seen a lot of viable treatment options. Following progression on first- and second-line treatments, there are notably very few treatment options for patients with advanced stage disease. However, vascular endothelial growth factor (VEGF) has become a point of notable interest for researchers in regard to targeted therapies in this disease type due to the role it plays in tumorigenesis and immunosuppression. Investigators believe axitinib could serve this unmet need due to the agent being a potent inhibitor of VEGF1, VEGF2, VEGF3, platelet‐derived growth factor receptor, and c-kit.

“These are patients with metastatic cancer for whom there are no good options outside of clinical trials,” Swiecicki said. “And it’s a very timely study because tyrosine kinase inhibitors like axitinib, which target tumors’ blood supply, have shown considerable synergy when combined with immunotherapy.”

The phase 2 trial evaluated axitinib within unresectable recurrent and metastatic HNSCC, utilizing the Choi criteria for assessment of radiographic response. The primary end point of the trial was 6-month overall survival.

A total of 29 patients were enrolled on the trial, 28 of whom were evaluable for response. The patient population included on the study was heavily pretreated with the majority having received ≥1 prior line of systemic therapy within the metastatic setting (61%; 95% CI, 0-5).

Correlative analyses revealed that patients with PI3K signaling pathway alterations had an increased response to the therapy (75%) compared to those who did not have PI3K alterations (17%). Patients who were treated with an immune checkpoint inhibitor following progression on axitinib also showed a notable degree of response to treatment.

Investigators believe that further examination of axitinib monotherapy or in combination with immunotherapy is needed within the portion of genomic biomarker-selected patients in order to further confirm its efficacy.

“Based on the mechanism of action of the drug, and what we know about how head and neck cancer grows, we were optimistic it could make a difference for head and neck cancer patients,” Swiecicki concluded.

Axitinib was first approved by the FDA in January 2012 for the treatment of advanced renal cell carcinoma (RCC) in patients who had progressed during a prior line of treatment. More recently, axitinib was approved in combination with immunotherapy agent avelumab (Bavencio) by the FDA in May 2019 as a frontline regimen for advanced RCC. The approval was based on the results of the pivotal phase 3 JAVELIN Renal 101 trial, which demonstrated a 31% reduction in the risk of disease progression or death compared with sunitinib (Sutent) regardless of PD-L1 expression.


  1. Swiecicki PL, Bellile EL, Brummel CV, et al. Efficacy of axitinib in metastatic head and neck cancer with novel radiographic response criteria. Cancer. 2020. doi:10.1002/cncr.33226.
  2. Axitinib improves survival for patients with incurable head and neck cancer. News release. M Health Lab. October 20, 2020. Accessed October 23, 2020.