In a phase 2 clinical trial for high-risk, resectable CSCC, Galloway, Das Neves, Amatore, et al. evaluated neoadjuvant treatment with two doses of pembrolizumab. Upon surgical resection, 56% of the 27 evaluable patients had a pathological complete response (PCR; no viable tumor remaining). While 81.5% patients continued on adjuvant pembrolizumab, 93.3% of those with PCR chose to forego adjuvant radiation, with no recurrences during a median follow-up of over 3 years. PCR was associated with post-treatment lymphoid aggregates of DCs, B cells, TCF1+CD8+ T cells, and HEVs. Non-response was associated with a TIME rich in PD-L1+ macrophages.
Contributed by Lauren Hitchings
Hugh Galloway1,13,16 ∙ Rodrigo X. Das Neves1,2,16 ∙ Florent Amatore1,2,16 ∙ Arivarasan Karunamurthy1,3 ∙ Samy Kotti1,2 ∙ Drew Hurd1,2 ∙ Shaum Sridharan4 ∙ Hong Wang1,5 ∙ Marion Joy6,7 ∙ Tanner Freeman6,7 ∙ Robert M. Morrison1,2 ∙ Mohammed A. Ghrib1,2 ∙ Terada Mitsuo1,2 ∙ Daniela Riccardi1,2 ∙ Anushri Kulkarni1,2 ∙ Ravi Patel1,8 ∙ Umamaheswar Duvvuri9 ∙ Seungwon Kim4 ∙ Kevin Contrera4 ∙ Haroon A. Choudry10 ∙ Matthew P. Holtzman10 ∙ James F. Pingpank10 ∙ Melissa Pugliano-Mauro11 ∙ Jeffrey R. Whiteaker12 ∙ Amy Rose1 ∙ Danielle Bednarz1 ∙ Amanda G. Paulovich12 ∙ John M. Kirkwood1,2 ∙ Yana G. Najjar1,2 ∙ Yufei Huang1,13,14 ∙ Hassane Zarour1,2,11,15,17 ∙ Diwakar Davar1,2,17,18
In a phase 2 clinical trial for high-risk, resectable CSCC, Galloway, Das Neves, Amatore, et al. evaluated neoadjuvant treatment with two doses of pembrolizumab. Upon surgical resection, 56% of the 27 evaluable patients had a pathological complete response (PCR; no viable tumor remaining). While 81.5% patients continued on adjuvant pembrolizumab, 93.3% of those with PCR chose to forego adjuvant radiation, with no recurrences during a median follow-up of over 3 years. PCR was associated with post-treatment lymphoid aggregates of DCs, B cells, TCF1+CD8+ T cells, and HEVs. Non-response was associated with a TIME rich in PD-L1+ macrophages.
Contributed by Lauren Hitchings
ABSTRACT: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer and a leading cause of non-melanoma skin cancer mortality. We conducted a phase 2 trial (NCT04808999) evaluating neoadjuvant pembrolizumab (200 mg intravenous [i.v.] every 3 weeks for 2 cycles) followed by surgery and adjuvant pembrolizumab in patients with high-risk resectable CSCC. The primary endpoint was pathologic complete response (PCR) by immune-related pathologic response criteria. Thirty patients were enrolled, and 27 underwent protocol-defined surgery and were evaluable for response. PCR was achieved in 15 patients (55.6%; 95% confidence interval [CI], 35.3%–74.5%) and was associated with a trend toward reduced 3-year recurrence risk (Gray’s p = 0.07). Adjuvant radiotherapy was omitted in 93.3% of PCR cases. Multiplex immunofluorescence and transcriptional analyses identified B cell- and dendritic cell-enriched lymphoid aggregates as correlates of PCR, whereas non-responders exhibited PD-L1-enriched macrophage- and tumor-dominant microenvironments. These findings support biomarker-driven treatment de-escalation strategies.
Author Info:
(1)- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA (2)- Division of Malignant Hematology and Oncology, Department of Medicine, Universit
y of Pittsburgh, Pittsburgh, PA, USA (3)- Division of Dermatopathology, Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA (4)- Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA (5)- Department of Biostatistics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA (6)- Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA (7)- NSABP Foundation, Inc., Pittsburgh, PA, USA (8)- Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA (9)- Department of Otolaryngology and Head and Neck Surgery, NYU Grossman School of Medicine, New York, NY, USA (10)- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA (11)- Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA (12)- Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA (13)- Department of Electrical and Computer Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA (14)- Department of Pharmaceutical Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA (15)- Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA (16)- These authors contributed equally (17)- Senior author (18)- Lead contact
