Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability–High Locally Advanced Rectal Cancer

Bando, Hideaki; Tsukada, Yuichiro; Inamori, Koji; Togashi, Yosuke; Koyama, Shohei; Kotani, Daisuke; Fukuoka, Shota; Yuki, Satoshi; Komatsu, Yoshito; Homma, Shigenori; Taketomi, Akinobu; Uemura, Mamoru; Kato, Takeshi; Fukui, Makoto; Wakabayashi, Masashi; Nakamura, Naoki; Kojima, Masaru; Kawachi, Hiroshi; Kirsch, Richard; Yoshida, Tsutomu; Suzuki, Yutaka; Sato, Akihiro; Nishikawa, Hiroyoshi; Ito, Masaaki; Yoshino, Takayuki

doi:10.1158/1078-0432.ccr-21-3213

Cited by 72 publications

(76 citation statements)

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“…The results of the VOLTAGE study, the first phase II trial of nivolumab in combination with preoperative chemoradiotherapy, have been reported [ 16 ]. According to this report, preoperative CRT followed by nivolumab and radical surgery was associated with only mild toxicity and increased the pCR rate, especially in patients with MSI-H (60 %) [ 16 ]. In our case, the course of treatment response suggested that TNT with nivolumab improved the outcome of patients with MSI-H for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…These reports suggest that the addition of immunotherapy to preoperative CRT may also be useful for LARC patients with dMMR and MSI-H. However, only one study has shown a benefit of preoperative CRT and nivolumab for LARC patients, and there are no reports showing the therapeutic effect of nivolumab in combination with TNT [ 16 ]. Therefore, we report a case of a patient with LARC with MSI-H who was treated with nivolumab in combination with TNT and achieved anus-preserving curative surgery.…”

Section: Introductionmentioning

confidence: 99%

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Locally advanced rectal cancer receiving total neoadjuvant therapy combined with nivolumab: a case report and literature review

et al. 2022

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Background The standard treatment for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, it has been suggested that intensification of neoadjuvant treatment with polychemotherapy in addition to CRT instead of as an adjuvant chemotherapy is better tolerated and associated with a higher pathological complete response (pCR) rate. This concept is known as total neoadjuvant therapy (TNT). Recently, the addition of immunotherapy to preoperative CRT has been reported to be useful in LARC patients with mismatch-repair-deficiency and high levels of microsatellite instability (MSI-H), but there are no reports showing the therapeutic effect of nivolumab in combination with TNT. Case presentation A 23-year-old man had frequent diarrhea. Preoperative examination revealed two adenocarcinomas in the rectum. His maternal grandmother had a rectal cancer patient who developed the disease at age 70s. The larger tumor was located at the peritoneal reflection, and its anterior border close to the prostate (<1 mm); there were eight enlarged pararectal lymph nodes. Considering the size and depth of the tumor, it was judged that radical resection with sufficient margins would be difficult. Therefore, it was decided that TNT would be performed. At first, CAPOX (capecitabine and L-OHP) was administered, followed by preoperative CRT (RT:50.4 Gy and capecitabine). During this period, genetic testing diagnosed this patient as MSI-H, so additional nivolumab was administered after CRT. Colonoscopy revealed that the larger tumor was no longer detectable, so robot-assisted intersphincteric resection and bilateral lateral lymph node dissection was performed. The diagnosis of pCR was made for the larger tumor and partial response was achieved for the smaller tumor, and no lymph node metastasis was found. Major complications were not observed and the patient was discharged on the 14th day after surgery. He was followed up without adjuvant chemotherapy and is alive and recurrence-free after 9 months. Conclusion A case of LARC with MSI-H was treated with TNT with nivolumab, resulting in pCR and complete radical resection. This result suggests that nivolumab in addition to TNT can be an option as a preoperative strategy for LARC with MSI-H.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Locally advanced rectal cancer receiving total neoadjuvant therapy combined with nivolumab: a case report and literature review

et al. 2022

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“…In the NICHE study [15], a major pathological response rate of 100% and an impressive pathological complete response (pCR) rate of 60% were reported. And in a study in patients with MSI-H rectal cancer, preoperative chemoradiotherapy plus nivolumab resulted in a pCR rate of 60% [16]. These indicate that anti-PD-1 immunotherapy may have the potential to become the curative treatment for dMMR/MSI-H rectal cancer.…”

Section: Introductionmentioning

confidence: 92%

Anti-PD-1-based immunotherapy as curative-intent treatment in dMMR/MSI-H rectal cancer: A multicentre cohort study

Wang

Xiao

Cheng

et al. 2022

European Journal of Cancer

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“…One of the studies showed the chemotherapy treatment was better among MSI-L/MSS compared to MSI-H which shows chemoresistance features in the colorectal cancer. Recently a clinical trial on advanced rectal tumour on MSS and MSI-H was conducted, preoperative chemoradiotherapy combined with Nivolumab showed promising result with complete pathological response in MSS and almost 60% in MSI-H, although the incidence of tumour with MSI-H status is low in distal colon [46]. Moreover, recurrent MSI-H tumour has been associated with immune response and developed mechanism to overcome the immunosurveillance.…”

Section: Surgical Implication and Chemotherapymentioning

confidence: 99%

Surgical Aspect of Microsatellite instability in Colorectal Cancer

2022

J Surg

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Approach to microsatellite instability associated colorectal cancer is a challenge faced by the surgeons. Various guidelines and implementation have been introduced to identify the microsatellite instability and MMR deficient status. Preoperative identification of the MSI status of the colorectal cancer by endoscopic, radiological guided and post operative surgical biopsy are important aspects for a surgeon and oncologist to make a strategic plan for the surgical intervention. Multiple factors need to be considered during the surgical decision keeping in view of the oncological response to the Microsatellite instability CRC treatment towards the chemotherapy and the new modulating immunotherapy. In this review we will briefly discuss the biological mechanism of the occurrence of MSI, the MSI testing results and its implementation on surgical aspects, and the current research on the immunotherapy response to the MSI in colorectal cancer.

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Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability–High Locally Advanced Rectal Cancer

Abstract: Financial support: The VOLTAGE study is an investigator-initiated investigational new drug (IND) clinical trial. A research grant and nivolumab were provided by Ono Pharmaceutical Co., Ltd.

Cited by 72 publications

References 44 publications

Locally advanced rectal cancer receiving total neoadjuvant therapy combined with nivolumab: a case report and literature review

Locally advanced rectal cancer receiving total neoadjuvant therapy combined with nivolumab: a case report and literature review

Anti-PD-1-based immunotherapy as curative-intent treatment in dMMR/MSI-H rectal cancer: A multicentre cohort study

Surgical Aspect of Microsatellite instability in Colorectal Cancer

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