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Diwakar Davar Reports 55.6% Pathologic Complete Response Rate with Pembrolizumab in cSCC
Diwakar Davar/LinkedIn

Diwakar Davar Reports 55.6% Pathologic Complete Response Rate with Pembrolizumab in cSCC

Diwakar Davar, Co-Leader of Cancer Immunology and Immunotherapy (CII) Program at UPMC Hillman Cancer Center, shared on LinkedIn:

“PD-1 blockade produces high rates of pathologic complete response (pCR) in high-risk resectable cutaneous squamous cell carcinoma (cSCC).

What we know:

  1. Neil Gross and colleagues showed that 2-4 doses of neoadjuvant cemiplimab produces ~50 pCR rates.
  2. This signal was further buttressed by work from Charlotte Zuur, Vasu Divi and Paolo Ascierto.
  3. Rahul Ladwa and colleagues went further. Using PET plus mapping biopsies to dynamically guide treatment, 48% of patients who received 4 cycles of pembrolizumab avoided both surgery and RT.

Our trial used just two doses of pembrolizumab before surgery in AJCC stage II-III LA cSCC. Results:

  1. In older Caucasian patients (median age 79), 55.6% pCR rate.
  2. RT was de-escalated in most (93%) of pCR patients.
  3. DFS may be a better way to measure success than RFS. RFS counts death from any cause as an event. In patients near 80, many of those deaths may not from cancer (2 of ours died of COVID-19 before surgery). Using competing-risks methods and disease-specific endpoints, we show that DFS was improved in pCR patients – separating ‘the cancer came back’ from ‘the patient died of something else.’
  4. A biology of response. Lymphoid aggregates comprising DCs cells and B cells that sustained TCF1+ CD8+ T cells identified using Lunaphore COMET drove response. Transcriptional and computational image analyses validated this signal in independent cohorts of cemiplimab-treated cSCC and in TCGA squamous cancers.

These trials used different drugs, doses and endpoints, so their numbers can’t be compared head to head. But together they make the same point: in cSCC, when you give PD-1 blockade matters, and so does how you measure the result.

The open questions now are about de-escalation and combinations.

  • Two doses or four?
  • Pathology, or PET plus biopsy?
  • Should disease-specific endpoints become the standard in this disease?
  • Can rational combinations targeting the immunosuppressive myeloid TME further increase pCR in cSCC?

More to come.

I’d value the views of surgeons, radiation oncologists, dermatopathologists, medical oncologists and biostatisticians. What would it take for you to omit RT after pCR.”

Title: Perioperative pembrolizumab in locally advanced cutaneous squamous cell carcinoma: A prospective phase 2 clinical trial

Authors: Hugh Galloway, Rodrigo X. Das Neves, Florent Amatore, Arivarasan Karunamurthy, Samy Kotti, Drew Hurd, Shaum Sridharan, Hong Wang, Marion Joy, Tanner Freeman, Robert M. Morrison, Mohammed A. Ghrib, Terada Mitsuo, Daniela Riccardi, Anushri Kulkarni, Ravi Patel, Umamaheswar Duvvuri, Seungwon Kim, Kevin Contrera, Haroon A. Choudry, Matthew P. Holtzman, James F. Pingpank, Melissa Pugliano-Mauro, Jeffrey R. Whiteaker, Amy Rose, Danielle Bednarz, Amanda G. Paulovich, John M. Kirkwood, Yana G. Najjar, Yufei Huang, Hassane Zarour, Diwakar Davar

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Amanda G. Paulovich Amy Rose Anushri Kulkarni Arivarasan Karunamurthy cancer immunotherapy cemiplimab cSCC cutaneous squamous cell carcinoma Daniela Riccardi Danielle Bednarz Diwakar Davar Diwakar Davar Read Drew Hurd Florent Amatore Haroon A. Choudry Hassane Zarour Hong Wang Hugh Galloway Immune Checkpoint Inhibitors immunotherapy James F. Pingpank Jeffrey R. Whiteaker John M. Kirkwood Kevin Contrera Locally Advanced cSCC Marion Joy Matthew P. Holtzman Melissa Pugliano-Mauro Mohammed A. Ghrib PD-1 blockade pembrolizumab Ravi Patel Robert M. Morrison Rodrigo X. Das Neves Samy Kotti Seungwon Kim Shaum Sridharan skin cancer Tanner Freeman Terada Mitsuo Umamaheswar Duvvuri Yana G. Najjar Yufei Huang