Dr Wong on Challenges Incorporating Checkpoint Inhibitors into Curative-Intent Regimens in HNSCC

Deborah J. Wong, MD, PhD, HS associate clinical professor, medicine, University of California, Los Angeles (UCLA) School of Medicine, UCLA Health, discusses challenges in integrating immune checkpoint inhibitors into curative treatment regimens for patients with head and neck squamous cell carcinomas (HNSCC).

Immune checkpoint inhibitors have an established role in the treatment of recurrent and metastatic HNSCC, Wong begins. However, efforts to move these therapies into the curative-intent setting for patients with high-risk disease have thus far been unsuccessful, she states. Wong details 3 phase 3 studies evaluating this approach that have failed to meet their primary end points: the JAVELIN Head and Neck 100 trial (NCT02952586) of avelumab (Bavencio) plus chemoradiotherapy (CRT) vs standard-of-care (SOC) chemoradiotherapy in patients with locally advanced HNSCC; the KEYNOTE-412 study (NCT03040999) of pembrolizumab (Keytruda) in the same patient population; and the IMvoke010 trial (NCT03452137), which evaluated patients with high-risk, locally advanced HNSCC who had undergone both surgical and non-surgical treatments and were treated with atezolizumab (Tecentriq).

Adding immune checkpoint inhibitors did not confer a significant benefit to patients being treated on these studies, Wong summarizes. Notably, the JAVELIN Head and Neck 100 trial was terminated in 2020 due to doubts about meeting the primary end point of progression-free survival (PFS). However, there is evidence of activity in this disease space, suggesting that further investigation is warranted, she notes. For example, a study presented at the 2024 ESMO Annual Congress indicated a potential benefit with sequential therapy when the immune checkpoint inhibitor was added following the completion of chemoradiation, Wong reports.

There is still much to learn about how and when to incorporate these agents in the curative-intent setting, Wong continues. One of the challenges highlighted by the IMvoke010 trial is the identification of patient subgroups that may benefit more from this treatment approach. IMvoke010 enrolled a heterogeneous population of patients who underwent varied treatment regimens, Wong details, adding that this diversity may have contributed to the trial's inability to demonstrate a clear benefit.

Future studies may need to focus on specific subpopulations that could derive more significant benefits from these therapies, she says. By analyzing the data from IMvoke010 and similar studies, researchers can identify potential subpopulations that might benefit more from immune checkpoint inhibitors. Redesigning studies with this refined focus could help determine the optimal use of these agents in the curative intent setting for patients with high-risk HNSCC, Wong concludes.