In a viewpoint published in the New England Journal of Medicine, Hanna K. Sanoff, MD, MPH, who is a Clinical Medical Director at UNC Lineberger Comprehensive Cancer Center and the quality and innovation officer of the North Carolina Cancer Hospital as well as a professor in the UNC School of Medicine Division of Oncology, provides a perspective on the evolving treatment of rectal cancer. [1]

In the article Sanoff offers a perspective for future treatment of the disease in light of encouraging findings from a study published in the journal that found the immunotherapy drug dostarlimab (Jemperli®, GlaxoSmithKline) was especially effective in a phase II clinical trial of a dozen patients with a subtype of rectal cancer. [2]

Approximately 5-10% of rectal cancers are molecularly characterized as being deficient in mismatch repair enzymes (dMMR). These cancers tend to be less responsive to chemotherapy and radiation, which increases the chance that surgical treatment is necessary.

Unfortunately, surgery can result in notable health consequences, including nerve damage, infertility, and bowel and sexual dysfunction.

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Rectal cancer
“Over 45,000 people in the United States were diagnosed with rectal cancer last year, and many of those cases were in people under the age of 65. Historical treatment of the disease has included radiation, surgery and chemotherapy, which can be debilitating despite its curative potential, pointing to the need for better and more effective treatments that can prolong longevity while maintaining quality of life,” Sanoff explained.

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Hanna K. Sanoff, MD, MPH is a Clinical Medical Director at UNC Lineberger Comprehensive Cancer Center and the quality and innovation officer of the North Carolina Cancer Hospital as well as a professor in the UNC School of Medicine Division of Oncology. Photo © 2020 – 2022 UNC Lineberger Comprehensive Cancer Center. Used with permission.

“These initial findings of the remarkable benefit with the use of dostarlimab are very encouraging but also need to be viewed with caution until the results can be replicated in a larger and more diverse population.”

Long-term
Sanoff also cautioned that little is known about how long the benefit of the drug will last or whether it will be curative in the long-term. Patients in this trial have only been observed for six months to two years so far.

“The responses in these first 12 of a planned-for 30 patients in the trial were remarkable and exceed what we would expect with the standard chemotherapy plus radiation,” Sanoff said. “Although quality of life measures have not been reported yet, it’s encouraging that some of the most difficult symptoms, such as pain and bleeding, all resolved with the use of dostarlimab.”

Sanoff noted there are other immunotherapy drugs that could also be tested against this form of rectal cancer.

“As a gastrointestinal medical oncologist, I can think of nothing better for my patients than being able to offer them a drug that is more effective, less toxic and avoids surgery, chemotherapy, and radiation; that day can’t come soon enough,” Sanoff concluded.

Results of the study were simultaneously published in New England Journal of Medicine and presented during the 2022 Annual Meeting of the American Society of Clinical Oncology.

Clinical trial
Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors – NCT04165772

Highlights of prescribing information
Dostarlimab (Jemperli®, GlaxoSmithKline)(Prescribing Information)

ASCO Abstract
Oaknin A, Pothuri B, Gilbert L, Sabatier R, Ghamande SA, Gravina A, Calvo E, Banerjee SN, et al. Dostarlimab in Advanced/Recurrent (AR) Mismatch Repair Deficient/Microsatellite Instability–High or Proficient/Stable (dMMR/MSI-H or MMRp/MSS) Endometrial Cancer (EC): The GARNET Study. Abstract 5509. J Clin Oncol 40, 2022 (suppl 16; abstr 5509) / DOI 10.1200/JCO.2022.40.16_suppl.5509

Hanlon J, Taylor Veneris J, Boklage S. Patient-reported outcomes from the GARNET trial in patients with advanced or recurrent mismatch repair deficient (dMMR) colorectal cancer (CRC): A post hoc subgroup analysis. Abstract #3558 / Poster #352. J Clin Oncol 40, 2022 (suppl 16; abstr 3558) / DOI 10.1200/JCO.2022.40.16_suppl.3558

Reference
[1] Sanoff HK. Improving Treatment Approaches for Rectal Cancer. N Engl J Med. 2022 Jun 5. doi: 10.1056/NEJMe2204282. Epub ahead of print. PMID: 35665785.
[2] Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 5. doi: 10.1056/NEJMoa2201445. Epub ahead of print. PMID: 35660797.

Featured image: Hanna K. Sanoff, MD, MPH is a Clinical Medical Director at UNC Lineberger Comprehensive Cancer Center and the quality and innovation officer of the North Carolina Cancer Hospital as well as a professor in the UNC School of Medicine Division of Oncology. Photo © 2020 – 2022 UNC Lineberger Comprehensive Cancer Center. Used with permission.

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