Stopping ICIs at 1 or 2 Years May Not Compromise Survival in HNSCC

Discontinuing ICIs in patients who were long-term responders to the therapy at 1 or 2 years may be reasonable without compromising survival, research showed.

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibition (ICI) had survival estimates that were similar to clinical trial results in the frontline and later settings, according to findings published in JAMA Network Open.

These findings also suggest that discontinuing ICIs in patients who were long-term responders to the therapy at 1 or 2 years may be reasonable without compromising survival.

The median overall survival (OS0 was 10.9 months (4.1-29.1) months, according to the study. In addition, OS was longer in patients who received ICI in the frontline setting (12.2 months; 4.8-32.0) compared to those in the second-line setting (8.7 months; 3.2-22.4) and third-line setting (9.1 months; 3.3-25.8).

Additionally, longer OS was also seen in patients with HPV-positive cancer (16.6 months vs 8.8 months) and an ECOG performance status 0 or 1 (13.5 months vs 5.5 months). There were no significant differences in survival between patients who stopped ICI at 1 or 2 years and those who continued with treatment.

“Establishing optimal treatment duration is important to avoid overtreatment and limit the substantial physical and financial toxicity associated with long-term or indefinite ICI treatment,” study authors wrote.

Notably, the median OS after ICI rechallenge was 15.7 months (13.7-21.9) in the immediate rechallenge group compared with 9.9 months (3.7-18.1) in the delayed rechallenge group.

These findings suggest the discontinuation of ICI in long-term responders at 1 or 2 years may prove useful, and the overall efficacy across subgroups continued to be beneficial. This study also reveals the similarities between prior clinical studies in all subgroups and the ability of ICI rechallenge to provide meaningful clinical benefit in some patients.

This retrospective, population-based cohort study included 4549 patients with recurrent or metastatic HNSCC who received ICI-containing therapy in any line of treatment. Among participants, 3551 (78.1%) were male, and the median (IQR) age was 66 (59-72) years. Additionally, common subsites of the disease included HPV-positive oropharynx (30.0%) and oral cavity (23.1%), followed by larynx (20.2%) and HPV-negative oropharynx (18.1%).

Of the patients in the study, 3000 (65.9%) received ICI in the frontline setting, followed by 1207 patients (26.5%) in the second-line setting and 3478 patients (76.5%) received ICI monotherapy.

Researchers assessed the outcomes of patients after ICI rechallenge, either as an immediate or delayed rechallenge. Immediate rechallenge, per the study, was defined as the start of an ICI-containing regimen after at least a 60-day period off of the therapy without an intervening non-ICI treatment. Delayed rechallenge, according to the researchers, was defined as a non-ICI line of therapy between initial ICI-containing line of therapy and another ICI-containing line of therapy.

The main outcome of this study was OS, defined as the time from the start of ICI treatment to death using the Kaplan-Meier method. Additionally, the study used Cox multivariable regression to determine the potential associations of key variables with survival, such as line of therapy, HPV status, and ECOG performance status.

Reference

Sun L, Cohen RB, D'Avella CA, Singh AP, Schoenfeld JD, Hanna GJ. Overall Survival, Treatment Duration, and Rechallenge Outcomes With ICI Therapy for Recurrent or Metastatic HNSCC. JAMA Netw Open. 2024;7(8):e2428526. Published 2024 Aug 1. doi:10.1001/jamanetworkopen.2024.28526