LBA 14 - Neoadjuvant and Adjuvant Pembrolizumab (Pembro) Plus Standard of Care (SOC) in Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC): Postoperative Risk Subgroup Analysis of KEYNOTE-689
Presenter(s)
N. Y. Lee1, D. Adkins2,3, R. I. Haddad4,5, Y. Tao6, C. Le Tourneau7, W. H. Westra8, R. Chernock9, M. Tahara10, K. Harrington11, A. Klochikhin12, R. Granado Carrasco13, G. V. Alves14, B. G. M. Hughes15, M. Oliva16, I. P. Figueiredo Lima17, T. Ueda18, C. Manschot19, K. Benjamin19, B. Gumuscu19, and R. Uppaluri20; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Robert Ebert and Greg Stubblefield Head and Neck Tumor Center, Alvin J. Siteman Cancer Center, and Barnes Jewish Hospital, St. Louis, MO, 3Washington University School of Medicine in St. Louis, St. Louis, MO, 4Dana-Farber Cancer Institute, Boston, MA, 5Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 6gustave roussy institute, villejuif, FL, France, 7Institut Curie, Paris, France, 8Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, 9Washington University School of Medicine, St Louis, MO, 10National Cancer Center Hospital East, Kashiwa, Japan, 11The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, London, United Kingdom, 12Yaroslavl Regional Clinical Oncology, Yaroslavl, Russian Federation, 13Vall d'Hebron Institute of Oncology (VHIO)/Vall d'Hebron University Hospital, Barcelona, Spain, 14Centro Integrado de Pesquisa em Oncologia, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, 15Royal Brisbane and Women’s Hospital and University of Queensland, Brisbane, Australia, 16Institut Català d’Oncologia, Barcelona, Spain, 17Centro Regional Integrado de Oncologia, Fortaleza, Brazil, 18Hiroshima University Hospital, Hiroshima, Japan, 19Merck & Co., Inc., Rahway, NJ, 20Department of Surgery/Otolaryngology, Brigham & Women's Hospital and Dana-Farber Cancer Institute, Boston, MA
Purpose/Objective(s): The addition of neoadjuvant and adjuvant (starting concurrently with postoperative radiotherapy [PORT] ± cisplatin) pembro to SOC significantly improved event-free survival (EFS) vs SOC alone for participants (pts) with resectable LA HNSCC in the randomized phase 3 KEYNOTE-689 study (NCT03765918). We present a subgroup analysis by postoperative pathological features.
Materials/Methods: Pts had resectable SCC of the oral cavity/larynx/hypopharynx (stage III/IVA) or oropharynx (stage III/IVA p16- or stage III T4 N0-2 p16+) and were randomized 1:1 to pembro 200 mg Q3W (2 cycles neoadjuvant, 3 cycles adjuvant concurrent with PORT, 12 cycles beyond PORT) + SOC vs SOC (surgery + PORT [60 Gy in 30 fractions for low risk or 66 Gy in 33 fractions for high risk] ± 3 cycles cisplatin 100 mg/m2 Q3W [high risk only]). Postoperative pathological features by blinded independent pathologist review were based on the presence (high risk) or absence (low risk) of positive margins (<1 mm) or extranodal extension. EFS by blinded independent central review with pembro + SOC vs SOC by risk subgroups was a prespecified exploratory analysis. Formal statistical testing was not planned. As of 25 July 2024, the median follow-up for all pts was 38.3 mo (range, 9.0–66.5).
Results: Among 363 pts randomized to pembro + SOC and 351 to SOC: 321 (88.4%) and 308 (87.7%) completed surgery; 118 (32.5%) and 156 (44.4%) had presence of high-risk features, and 196 (54.0%) and 148 (42.2%) did not. 274 pts in the pembro + SOC group and 275 in the SOC group received PORT, of whom 107 and 139 pts also received concurrent cisplatin (median 3 cycles in both groups). Median (range) total PORT dose was 60.0 Gy (2.0–70.0) in the pembro + SOC group and 66.0 Gy (6.0–72.0) in the SOC group.
In the high-risk subgroup, median EFS was 41.1 vs 19.5 mo, respectively (HR 0.73, 95% CI 0.52–1.05). The 3-year EFS was 52.0% vs 40.7%. Grade =3 TRAEs occurred in 52.1% vs 53.9% of pts. Any-cause AEs led to discontinuation of PORT in 3 pts in the pembro + SOC group and 1 pt in the SOC group. In the low-risk subgroup, median EFS was not reached vs 51.5 mo (HR 0.74, 95% CI 0.51–1.08). The 3-year EFS was 67.7% vs 58.8%. Grade =3 TRAEs occurred in 42.9% vs 30.4% of pts. Any-cause AEs led to discontinuation of PORT in 4 pts in the pembro + SOC group and 3 pts in the SOC group.Conclusion: Efficacy results for pts with either presence or absence of high-risk pathological features after surgery demonstrated downgrading of pathological features with the addition of neoadjuvant and adjuvant pembro to SOC, consistent with the primary analysis of KEYNOTE-689. In the pembro + SOC group, fewer pts had high-risk pathological features and more pts received a lower radiation dose and no cisplatin. The safety profile of pembro + PORT ± cisplatin was in line with expectations.