Immunotherapy completely disappeared in 14 patients with advanced rectal cancer!

• Facebook
• Twitter
• Reddit
• Tumblr
• LinkedIn
• Pinterest
• RSS Feed
• Link

• Red Yeast Rice Scare Grips Japan: Over 114 Hospitalized and 5 Deaths
• Long COVID Brain Fog: Blood-Brain Barrier Damage and Persistent Inflammation
• FDA has mandated a top-level black box warning for all marketed CAR-T therapies
• Can people with high blood pressure eat peanuts?
• What is the difference between dopamine and dobutamine?
• How long can the patient live after heart stent surgery?

NEJM: Immunotherapy completely disappeared in 14 patients with advanced rectal cancer!

About 5%-10% of rectal cancer patients have dMMR. The incidence of rectal cancer in young people of reproductive age is on the rise. “The elimination of tumors after 6 months of PD-1 immunotherapy in this study allowed us to omit chemoradiotherapy and surgery and just observe,” said a doctor from the MSKCC clinical trial team.

Such a state has a huge impact on the patient’s quality of life, as standard chemoradiotherapy can affect the fertility of young patients. PD-1 immunotherapy may confer particular benefits in this age group.

Dotalizumab has previously been approved by the US FDA for the treatment of dMMR-positive recurrent or advanced endometrial cancer.  Rectal cancer is for off-label use.

All patients in this study had stage 2 or 3 rectal adenocarcinoma with mismatch repair deficiency, tumors that did not respond well to standard chemotherapy regimens , including neoadjuvant chemotherapy .

The median age of enrolled patients was 54 years, and 62% were women. All patients received dotalimumab monotherapy every 3 weeks for 6 months.

The report showed that patients responded quickly to treatment, with 81% of patients experiencing symptom relief within 8 weeks of starting dostarlimab.

To date, 4 patients have achieved sustained clinical complete remission 1 year after completing the anti-PD-1 course.

Adverse reactions occurred in most patients with dotalimumab treatment, but none were grade 3 or higher.

The most common grade 1-2 adverse reactions were rash or dermatitis, pruritus, fatigue, nausea, and thyroid dysfunction occurred in one patient.

The researchers plan to enroll 30 patients with stage II/III dMMR rectal cancer.

The primary objectives were overall response rate with single-agent dostarlimab with or without chemoradiotherapy, and pathological complete response or clinical complete response at 12 months after PD-1 inhibition, with or without chemoradiotherapy.

Rectal MRI and endoscopy determined stable disease and response (partial, near-complete, and complete) .

Clinical complete remission was defined by endoscopy, digital rectal examination, and rectal MRI.

The median age of the first 18 patients was 54 years, and 12 of them were women.

Fourteen patients had T3/4 tumors, and all but one had one or more involved lymph nodes.

Ten of the 17 evaluable patients had germline mutations, and all 18 were BRAF V600E wild-type.

Of the first 14 patients, 12 had a clinical complete response at 6 months of follow-up, of which 2 patients met the criteria for a complete response at 3 months.

The remaining four patients did not reach the 6-month follow-up, but one patient had met the criteria for a clinical complete response.

This therapy is still in the experimental stage, and the long-term efficacy and risk of recurrence are unclear.

Relapse occurs when immunotherapy with PD-1 drugs is used for dMMR-positive metastatic colorectal cancer.

For example, in the KEYNOTE-177 trial using another PD-1 antibody , pembrolizumab ( Keytruda), only about 55% of colorectal cancer patients were alive without cancer progression at 12 months, compared with initial treatment response.

Only 70% of the significant and intense patients showed a sustained efficacy response after 3 years.

Therefore, in order to further judge the long-term efficacy, very close monitoring and observation of patients are required.

The current study, conducted at the top cancer center, Memorial Sloan Kettering Cancer Center, used a combination of rectal MRI, visual endoscopy and digital rectal examination to judge complete responses.

The accuracy of the response was further supported by the absence of residual tumor cells in serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake in PET scans.

“No patients required chemotherapy, radiation, or surgery, and no disease recurrence was observed during follow-up,” Andrea Cercek, MD, said in the data presentation. “Longer follow-up is definitely needed to determine the durability of this treatment. Taken together, we believe these data provide a framework for immune clearance therapies. It highlights the clinical impact of biomarker-driven therapies, in other words, bringing precision medicine to the fore. Metastases into early-stage disease.”

Cercek is chief of the Colorectal Cancer Unit at Memorial Sloan Kettering Cancer Center in New York and co-director of the Center for Young-Onset Colorectal and Gastrointestinal Cancers.

References:

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

Immunotherapy completely disappeared in 14 patients with advanced rectal cancer!

(source:internet, reference only)

Disclaimer of medicaltrend.org

Important Note: The information provided is for informational purposes only and should not be considered as medical advice.