AIMS: The activity that the immune checkpoint inhibitor (ICI) cemiplimab has recently demonstrated has led to a paradigm shift in the management of patients with advanced cutaneous squamous cell carcinoma (cSCC). To identify predictive biomarkers of response to ICIs in advanced cSCC, we studied 33 patients who received ICI therapy at the Dana-Farber/Harvard Cancer Center (DF/HCC) and analysed sequencing data for a subset of these patients. METHODS: We collected clinical data using electronic health records and genomic data using the institutional OncoPanel platform of the DF/HCC. We compared tumour genomics with data from previously sequenced cSCC cohorts. RESULTS: We observed high tumour mutational burden regardless of smoking status and response to ICI and longer median overall survival among those patients who achieved an ICI response. We compared the genetic data from our cohort with data from other cohorts that included fewer patients with distant metastatic disease. Although our cohort had a similar genetic landscape to those of comparator cohorts, mutations in PIK3C2B were more common in our study. In our cohort, copy number alterations (CNAs) in the 3q chromosomal arm appeared to predict response to ICI therapy. CONCLUSION: CNAs in the 21-27 bands of chromosome arm 3q, a region that includes PIK3CA, ETV5 and BCL6, may represent predictors of response to ICI and may be candidates for drug targeting in combination or sequence with ICI agents.
AIMS: The activity that the immune checkpoint inhibitor (ICI) cemiplimab has recently demonstrated has led to a paradigm shift in the management of patients with advanced cutaneous squamous cell carcinoma (cSCC). To identify predictive biomarkers of response to ICIs in advanced cSCC, we studied 33 patients who received ICI therapy at the Dana-Farber/Harvard Cancer Center (DF/HCC) and analysed sequencing data for a subset of these patients. METHODS: We collected clinical data using electronic health records and genomic data using the institutional OncoPanel platform of the DF/HCC. We compared tumour genomics with data from previously sequenced cSCC cohorts. RESULTS: We observed high tumour mutational burden regardless of smoking status and response to ICI and longer median overall survival among those patients who achieved an ICI response. We compared the genetic data from our cohort with data from other cohorts that included fewer patients with distant metastatic disease. Although our cohort had a similar genetic landscape to those of comparator cohorts, mutations in PIK3C2B were more common in our study. In our cohort, copy number alterations (CNAs) in the 3q chromosomal arm appeared to predict response to ICI therapy. CONCLUSION: CNAs in the 21-27 bands of chromosome arm 3q, a region that includes PIK3CA, ETV5 and BCL6, may represent predictors of response to ICI and may be candidates for drug targeting in combination or sequence with ICI agents.
Authors: Binsheng Gong; Dan Li; Rebecca Kusko; Natalia Novoradovskaya; Yifan Zhang; Shangzi Wang; Carlos Pabón-Peña; Zhihong Zhang; Kevin Lai; Wanshi Cai; Jennifer S LoCoco; Eric Lader; Todd A Richmond; Vinay K Mittal; Liang-Chun Liu; Donald J Johann; James C Willey; Pierre R Bushel; Ying Yu; Chang Xu; Guangchun Chen; Daniel Burgess; Simon Cawley; Kristina Giorda; Nathan Haseley; Fujun Qiu; Katherine Wilkins; Hanane Arib; Claire Attwooll; Kevin Babson; Longlong Bao; Wenjun Bao; Anne Bergstrom Lucas; Hunter Best; Ambica Bhandari; Halil Bisgin; James Blackburn; Thomas M Blomquist; Lisa Boardman; Blake Burgher; Daniel J Butler; Chia-Jung Chang; Alka Chaubey; Tao Chen; Marco Chierici; Christopher R Chin; Devin Close; Jeffrey Conroy; Jessica Cooley Coleman; Daniel J Craig; Erin Crawford; Angela Del Pozo; Ira W Deveson; Daniel Duncan; Agda Karina Eterovic; Xiaohui Fan; Jonathan Foox; Cesare Furlanello; Abhisek Ghosal; Sean Glenn; Meijian Guan; Christine Haag; Xinyi Hang; Scott Happe; Brittany Hennigan; Jennifer Hipp; Huixiao Hong; Kyle Horvath; Jianhong Hu; Li-Yuan Hung; Mirna Jarosz; Jennifer Kerkhof; Benjamin Kipp; David Philip Kreil; Paweł Łabaj; Pablo Lapunzina; Peng Li; Quan-Zhen Li; Weihua Li; Zhiguang Li; Yu Liang; Shaoqing Liu; Zhichao Liu; Charles Ma; Narasimha Marella; Rubén Martín-Arenas; Dalila B Megherbi; Qingchang Meng; Piotr A Mieczkowski; Tom Morrison; Donna Muzny; Baitang Ning; Barbara L Parsons; Cloud P Paweletz; Mehdi Pirooznia; Wubin Qu; Amelia Raymond; Paul Rindler; Rebecca Ringler; Bekim Sadikovic; Andreas Scherer; Egbert Schulze; Robert Sebra; Rita Shaknovich; Qiang Shi; Tieliu Shi; Juan Carlos Silla-Castro; Melissa Smith; Mario Solís López; Ping Song; Daniel Stetson; Maya Strahl; Alan Stuart; Julianna Supplee; Philippe Szankasi; Haowen Tan; Lin-Ya Tang; Yonghui Tao; Shraddha Thakkar; Danielle Thierry-Mieg; Jean Thierry-Mieg; Venkat J Thodima; David Thomas; Boris Tichý; Nikola Tom; Elena Vallespin Garcia; Suman Verma; Kimbley Walker; Charles Wang; Junwen Wang; Yexun Wang; Zhining Wen; Valtteri Wirta; Leihong Wu; Chunlin Xiao; Wenzhong Xiao; Shibei Xu; Mary Yang; Jianming Ying; Shun H Yip; Guangliang Zhang; Sa Zhang; Meiru Zhao; Yuanting Zheng; Xiaoyan Zhou; Christopher E Mason; Timothy Mercer; Weida Tong; Leming Shi; Wendell Jones; Joshua Xu Journal: Genome Biol Date: 2021-04-16 Impact factor: 13.583