25 september 2022: Bron: NEJM, September 12, 2022

Immuuntherapie met cemiplimab vooraf aan een operatie bij patiënten met huidkanker van het type cutaan plaveiselcarcinoom blijkt succesvolle aanpak en gaf bij 40 van de 79 deelnemende patiënten (51 procent - 95% confidence interval , 39 to 62) een via scans bevestigde complete remissie. Bij 10 andere patiënten (13 procent - 95% CI, 6 to 22) deed zich een partiële remissie voor waarbij slechts minder dan 10 procent kankercellen waren overgebleven voordat de operatie werd uitgevoerd.
Bij scans vooraf direct aan de operatie vertoonden 54 patiënten (68 procent) een objectieve respons. Bijwerkingen tijdens het onderzoek traden op bij 69 patiënten (87 procent) en bijwerkingen van graad 3 of hoger traden op bij 14 patiënten (18 procent).

In vergelijking met historische data voor dit type van huidkanker en bij deze patiëntengroep (stadium II, III, of IV zonder uitzaaiingen) was 25 procent complete remissies verwacht. Met deze aanpak werd dus het dubbele aan complete remissies bereikt in vergelijking met historische data.

Deze resultaten uit een fase II studie werden gepresenteerd op ESMO 2022 (the European Society for Medical Oncology, held Sept. 9 to 13 in Paris).

Een gevorderd stadium van huidkanker van het type cutaan plaveiselcarcinoom wordt meestal behandeld met een operatie gevolgd door bestraling - radiotherapie. De gevolgen van deze aanpak kunnen soms leiden tot ernstige functionele beperkingen en/of verminkingen en het effect hiervan op de kwaliteit van leven van patiënten is soms groot.

Voor systemische therapie bij de behandeling van operabele plaveisel carcinoom is meestal geen interesse omdat operatieve ingrepen vaak toch wel voor goede resultaten zorgen.
Maar nu blijkt uit deze studie waarbij meer dan de helft van de patiënten een volledige pathologische respons bereikt hadden na twee doses immuuntherapie voorafgaand aan de operatie dat een systemische aanpak wel degelijk de moeite waard kan zijn.

Het volledige studierapport is tegen betaling in te zien of te downloaden. Hier het abstract van de studie zoals gepresenteerd op ESMO 2022:

Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma

Neil D. Gross, M.D.,
David M. Miller, M.D., Ph.D.,
Nikhil I. Khushalani, M.D.,
Vasu Divi, M.D.,
Emily S. Ruiz, M.D., M.P.H.,
Evan J. Lipson, M.D.,
Friedegund Meier, M.D.,
Yungpo B. Su, M.D.,
Paul L. Swiecicki, M.D.,
Jennifer Atlas, M.D.,
Jessica L. Geiger, M.D.,
Axel Hauschild, M.D.,

Abstract

BACKGROUND

In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings.

METHODS

We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events.

RESULTS

A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval , 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%).

CONCLUSIONS

Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943. opens in new tab.)

Supported by Regeneron Pharmaceuticalsand Sanofi.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on September 12, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the patients, their families, and all staff members at the study sites who were involved in this study; and Atif Riaz, Ph.D., of Prime (Knutsford, United Kingdom) for medical-writing support, funded by Regeneron Pharmaceuticals.

Author Affiliations

From the Department of Head and Neck Surgery (N.D.G.) and the Department of Thoracic and Head and Neck Medical Oncology (R.F.), M.D. Anderson Cancer Center, Houston, and the Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas (J.H.); the Department of Medicine, Division of Hematology and Oncology (D.M.M.), the Department of Dermatology (D.M.M.), and the Department of Surgery (H.L.K.), Massachusetts General Hospital and Harvard Medical School, and the Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School (E.S.R.) — all in Boston; the Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL (N.I.K.); the Department of Otolaryngology–Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA (V.D.); Bloomberg–Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center (E.J.L., J.M.T.) and the Department of Dermatology, School of Medicine (J.M.T.), Johns Hopkins University, Baltimore; the Skin Cancer Center at the University Cancer Center and the National Center for Tumor Diseases Dresden, Department of Dermatology, University Hospital Carl Gustav Carus and Technische Universität Dresden, Dresden (F.M.), the Department of Dermatology, Schleswig-Holstein University Hospital, Kiel (A.H.), and the Department of Dermatology, University Hospital of Essen and German Cancer Consortium, Partner Site Essen, Essen (D.S.) — all in Germany; Head and Neck Medical Oncology, Nebraska Cancer Specialists, Omaha (Y.B.S.); Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor (P.L.S.); Levine Cancer Institute, Atrium Health, Charlotte (J.A.), and Duke Cancer Institute, Durham (J.H.C.) — both in North Carolina; Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland (J.L.G.); the Department of Cancer Care Services, Royal Brisbane and Women’s Hospital and University of Queensland, Brisbane (B.G.M.H.), and the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (A.M.L., D.R.) — both in Australia; the Departments of Dermatology, Medicine, and Oncology, George Washington University School of Medicine and Health Sciences, Washington, DC (V.A.P.); and Regeneron Pharmaceuticals, Tarrytown, NY (F.S., I.L., S.-Y.Y., M.M., K.F., H.H., M.G.F.).

Dr. Gross can be contacted at ngross@mdanderson.org or at M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

immuuntherapie, cemiplimab, huidkanker type cutaan plaveiselcelcarcinoom, complete remissie, partiele remissie