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Home > Oncology > ASCO 2022 > Gastrointestinal Cancers > Spectacular results for dostarlimab in mismatch repair deficient rectal cancer 

Spectacular results for dostarlimab in mismatch repair deficient rectal cancer 

Presented by
Dr Andrea Cercek, Memorial Sloan Kettering Cancer Center, NY, USA
Conference
ASCO 2022
Doi
https://doi.org/10.55788/a3fc7a36

    A phase 2 trial investigating neoadjuvant treatment with the PD-1 inhibitor dostarlimab in patients with stage II or III mismatch repair deficient (dMMR) rectal cancer showed a response rate of 100% following treatment with this agent in the thus far analysed patients. Off-protocol use of neoadjuvant immunotherapy in this population is likely to occur.  

    “Locally advanced rectal cancer is treated with a combination of chemotherapy, radiation, and optional surgery, with all its costs and life-altering consequences,” said Dr Andrea Cercek (Memorial Sloan Kettering Cancer Center, NY, USA) [1]. Patients with dMMR rectal cancer are relatively resistant to chemotherapy but are responsive to checkpoint inhibitors [2,3]. The current phase 2 study aimed to assess whether neoadjuvant PD-1 inhibition may be able to replace chemotherapy, chemo- and radiation therapy, or chemotherapy, radiation therapy, and surgery in patients with dMMR rectal cancer.

    For this purpose, 30 patients received dostarlimab (500 mg, intravenous, every 3 weeks) for 6 months followed by radiologic and endoscopic evaluation. If a clinical complete response was achieved, a wait-and-see approach was installed with 4-monthly follow-up visitations. If residual disease was detected, patients received chemoradiation. After completion of this therapy, another evaluation would decide if surgery was needed. The primary objectives were the overall response rate of PD-1 blockade with or without chemoradiation and the pathologic or clinical complete response rate at 12 months after PD-1 therapy with or without chemoradiation.

    Spectacularly, all 14 patients that have been analysed to date reached a clinical complete response on dostarlimab therapy alone. Moreover, the responses were ongoing in all assessed patients after a median follow-up of 6.8 months (see Figure). Furthermore, no grade 3 or 4 adverse events were reported in these patients.

    Figure: Duration of clinical complete response on dostarlimab treatment [3]



    According to Dr Cercek, PD-1 inhibition may eliminate the need for chemotherapy and radiation in patients with early-stage dMMR rectal cancer and may rapidly translate to areas without access to modern chemotherapy, radiation, and surgery. It will spare patients from toxicity and late effects of chemo- and radiation therapy and surgery.

    “Based on the data of this study, off-protocol use of neoadjuvant immunotherapy in this population is likely to occur,” expected Dr Kimmie Ng (Dana-Farber Cancer Institute, MA, USA), who commented on this late-breaking abstract. Dr Ng commented that the results are spectacular, but that larger sample sizes, longer follow-up time, and results from other endpoints are needed before standard-of-care may be changed in this population.

    1. Cercek A, et al. Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer. LBA5, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.
    2. Cercek A, et al. Clin Can Res. 2020;26(13):3271‒3279.
    3. Andre T, et al. NEJM. 2020;383;2207–2218. 

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