Atezolizumab with bevacizumab, paclitaxel and carboplatin was effective for patients with SMARCA4-deficient thoracic sarcoma

• Published in: Immunotherapy 2021-07, Vol.13 (10), p.799-806
• Main Authors: Kawachi, Hayato, Kunimasa, Kei, Kukita, Yoji, Nakamura, Harumi, Honma, Keiichiro, Kawamura, Takahisa, Inoue, Takako, Tamiya, Motohiro, Kuhara, Hanako, Nishino, Kazumi, Mizote, Yu, Akazawa, Takashi, Tahara, Hideaki, Kumagai, Toru
• Format: Article
• Language: English
• Subjects: atezolizumab; bevacizumab; immunotherapy; SMARCA4-DTS; SMARCA4-DTST
• ISSN: 1750-743X; 1750-7448
• DOI: 10.2217/imt-2020-0311

SMARCA4-deficient thoracic sarcoma (DTS) is a recently noted progressive thoracic malignancy. We recently experienced three cases of SMARCA4-DTS who were treated with atezolizumab in combination with bevacizumab, paclitaxel and carboplatin (ABCP) as the first-line therapy. Immunohistopathological analysis revealed absent expression of SMARCA4 in all cases. The tumor mutational burden was over 11/Mb and mutations in and were detected in all three cases. Partial response to ABCP treatment was observed in all three cases, with a progression-free survival of approximately 6 months or longer and a continuous response of 1 year or longer in one case. The first-line ABCP treatment demonstrated durable efficacy in SMARCA4-DTS regardless of the degree of PD-L1 expression. Lung cancer is the leading cause of cancer-related death worldwide. Among them, SMARCA4-deficient thoracic sarcoma (DTS), which lacks SMARCA4 expression and exhibits an undifferentiated carcinoma histology, is a recently identified subtype of lung cancer. It tends to occur in younger people with heavy smoking status and has been reported to recur quickly and have a poor prognosis even after chemotherapy, radiation therapy or surgery. There is no effective molecularly targeted agent for SMARCA4-DTS and the identification of an effective therapy is required. Here, we report the clinical features and genomic information of three SMARCA4-DTS cases in which atezolizumab with bevacizumab, paclitaxel and carboplatin treatment was effective. This report suggests the efficacy of atezolizumab with bevacizumab, paclitaxel and carboplatin treatment compared with conventional chemotherapy.