KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy of RT in patients with SCCHN who have progressed on anti-PD-1 directed therapy.
- The primary endpoint was to determine PFS.
- Researchers noticed promising outcomes in recurrent/metastatic squamous cell carcinoma of the head and neck patients following disease oligo-progression on prior anti-PD-1 therapy.
Treatment options for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who have progressed on anti-PD-1-directed therapy are severely restricted. Some patients exhibit limited disease progression, termed oligo-progression, which may render them suitable candidates for radiation therapy (RT). However, RT has not undergone prospective testing in this specific patient population.
Yu-Hui Chen and the team aimed to assess the potential efficacy of RT in recurrent/metastatic SCCHN patients with oligo-progression following anti-PD-1 therapy.
Researchers performed an inclusive analysis of a phase 2 trial investigation focused on RT with concurrent pembrolizumab (pembro) in patients with SCCHN whose disease progressed on prior PD-1 blockade. Cohort A allowed RT to a single lesion, while Cohort B allowed RT to up to 6 lesions.
The primary endpoint was overall progression-free survival (PFS) at 3 months (mo). A two-stage design was used in each cohort to distinguish 3-mo PFS >65% vs. 35%. Cytometry by time of flight (CyTOF) evaluated circulating immune populations in peripheral blood samples obtained at baseline and over the course of therapy.
About 18 patients were enrolled, with 6 in Cohort A and 12 in Cohort B. Approximately 44% of patients had HPV+ disease, with 16 receiving prior chemoRT to the HN. The median number of metastases was 8.5 for Cohort A and 2 for Cohort B. The most common protocol RT dose was 40 Gy in 5 fractions, predominantly targeting head and neck and lung sites.
Treatment was generally well-tolerated, with grade 3 and 4 toxicities primarily observed in Cohort B. Median PFS for Cohort A was 1.8 mo, with one patient progression-free at 3 mo, leading to non-progression to the second stage.
In Cohort B, the median PFS was 6.5 mo, and a significant association was found between PFS and a smaller RT target, number of metastases, and extent of RT. Median OS was 7.6 and 10.2 mo for Cohorts A and B, respectively. CyTOF analysis revealed elevated circulating CD8+ central memory T-cell levels and CXCR5 expression in memory B-cells from patients with PFS > 3 mo.
The study concluded that RT in R/M SCCHN patients following disease oligo-progression on prior anti-PD-1 therapy resulted in more promising outcomes, particularly when RT targeted the majority/entirety of measurable disease, with a median PFS exceeding 6 months. Multiplexed immune cell measurements identified potential biomarkers for selecting patients who may benefit from integrated RT following progression on anti-PD-1 therapy.
The study is sponsored by Dana-Farber Cancer Institute
Source: https://astro.confex.com/astro/hncs2024/meetingapp.cgi/Paper/59456
Clinical Trial: https://clinicaltrials.gov/study/NCT03085719
Chen Y H, Droznin A, Nau A, et al. (2024). “A Phase 2 Clinical Trial of Pembrolizumab with Radiation Following Progression on anti-PD-1 Therapy in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck.” Presented at MHNCS 2024 (Abstract 140).
