Chemoradiotherapy De-escalation Appears Feasible in HPV+ Oropharynx Cancer

“We plan to continue to investigate the role of multimodal approaches for de-escalation of therapy for this patient population,” according to Samuel Regan, MD.

Deescalating chemoradiotherapy (CRT) based on FDG-PET appeared feasible and yielded few regional recurrences in patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC), according to findings from a phase 2 trial presented at the 2024 American Society for Radiation Oncology (ASTRO) Multidisciplinary Head and Neck Cancers Symposium.

With a median follow-up of 32.1 months, the 2-year locoregional recurrence (LRR) rate was 6.8% (90% CI, 1.8%-11.5%) across the entire study cohort. Additionally, for patients receiving 70 Gy (n = 2), the 2-year LRR rate was 4.6% (90% CI, 0.0%-9.8%) and 9.4% (90% CI, 0.5%-17.6%) in those who received 54 Gy (n = 3).

The 2-year progression-free survival (PFS) rate in the overall population was 87% (90% CI, 81%-94%). Radiation at 70 Gy yielded a 2-year PFS rate of 89% (90% CI, 82%-97%); treatment failed 4 patients, and there was 1 death that was determined to be likely associated with treatment. Among patients who received 54 Gy of radiation, the 2-year PFS rate was 84% (90% CI, 74%-96%); treatment failed 4 patients in this group.

The median loss of weight from baseline to 3 months following radiotherapy was 23 lbs (IQR, 15-35) in the standard radiotherapy cohort compared with 11 lbs (IQR, 7-17) in the de-escalated radiation cohort (P <.001). Between radiotherapy and 1 month following treatment, feeding tube use was highlighted in 16% and 11% of patients in each respective cohort (P = .5); no patients required a feeding tube at 3 months following radiation. There were no significant changes in penetration-aspiration scale (PAS) scores in the standard and de-escalation cohorts from baseline to 3 months (P = .094) or 12 months (P = .2).

At 1 month, the difference in estimated mean University of Washington Quality of Life (UWQOL) scores in the de-escalated vs standard radiotherapy arm was –3.03, and the standardized effect size (ES) was –0.61 (P = .01). The estimated mean difference in pain subscale scores between arms was –5.98, and the standardized ES was –0.90 (P <.001).

The estimated mean difference in total Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) scores at 1 month in the de-escalated vs standard radiation arm was 9.09 with a standardized ES of 0.51 (P = .03). The estimated mean difference for the cancer subscale scores was 4.90, and the standardized ES was 0.78.

“We plan to continue to investigate the role of multimodal approaches for de-escalation of therapy for this patient population,” Samuel Regan, MD, a PGY-3 resident at The University of Michigan Radiation Oncology Residency Program, said in a presentation on these findings.

According to Regan, the study was inspired by a lack of prospectively validated predictive biomarkers for responses to CRT in patients with HPV-positive OPSCC. FDG-PET was hypothesized to be an effective imaging biomarker in this population due to findings from observational studies indicating that FDG-PET metrics during treatment correlated with oncologic end points.

The phase 2 study included patients with stage I or II p16-positive OPSCC and FDG-PET avid disease; those who received prior surgery or radiotherapy for head and neck cancer or had matted lymph nodes or cT0 disease were not able to enroll. Following a pre-treatment PET scan, patients began radiation at 70 Gy to gross disease and 56 Gy to elective lymph nodal regions concurrently with weekly carboplatin/paclitaxel. Patients then underwent a mid-treatment PET scan; those with a less than 50% decrease in metabolic tumor volume (MTV)2.5 were assigned to receive subsequent standard CRT, and those with a 50% or higher decrease in MTV2.5 were assigned to receive de-escalated CRT.

Patients in the standard CRT arm (n = 48) received 70 Gy to gross disease and 56 Gy to elective nodal regions in 35 fractions. Additionally, those in the de-escalated treatment arm (n = 36) received 54 Gy to gross disease plus 43.2 Gy to elective nodal regions in 27 fractions.

The study’s primary end point was non-inferiority of 2-year LRR rates of the entire cohort compared with those observed in a historical control group. Secondary end points highlighted in the presentation included patterns of failure and survival as well as patient-reported outcomes.

The median age was 60 years (IQR, 54-69) in the standard radiation arm and 60 years (IQR, 52-67) in the de-escalated radiation arm (P = .7). Most patients in each respective arm were male (88% vs 94%; P = .5), had stage I disease (71% vs 81%; P = .3), stage T1 disease (46% vs 47%; P = .2), and stage N1 disease (81% vs 86%; P = .7). Most patients in the standard radiation group had tumors on the tonsil (52%), and most in the de-escalated radiation arm had tumors on the base of the tongue (53%).

Reference

Regan SN, Rosen BS, Suresh K, et al. FDG-PET-based selective de-escalation of radiotherapy for HPV-related oropharynx cancer: results from a phase II trial. Presented at the 2024 American Society for Radiation Oncology Multidisciplinary Head and Neck Cancers Symposium; February 29-March 2, 2024; Phoenix, Arizona. Abstract 16.