PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer.

@article{Cercek2022PD1BI,
  title={PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer.},
  author={Andrea Cercek and Melissa A Lumish and Jenna Sinopoli and Jill Weiss and Jinru Shia and Michelle F Lamendola-Essel and Imane El Dika and Neil H. Segal and Marina Shcherba and Ryan Sugarman and Zsofia K. Stadler and Rona Yaeger and J. Joshua Smith and Beno{\^i}t Rousseau and Guillem Argil{\'e}s and Miteshkumar Patel and Avni Mukund Desai and Leonard B. Saltz and Maria Widmar and Krishna Iyer and Janie Y Zhang and Nicole Gianino and Christopher Crane and Paul B. Romesser and Emmanouil P. Pappou and Philip P. Paty and Julio Garcia-Aguilar and Mithat Gonen and Marc J. Gollub and Martin R. Weiser and Kurt A. Schalper and Luis A. Diaz},
  journal={The New England journal of medicine},
  year={2022}
}
BACKGROUND Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced… 

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References

SHOWING 1-10 OF 24 REFERENCES

Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative manageme

This study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR, and is the first NOM trial utilizing a regression schema for response assessment in a prospective fashion.

Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer.

FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers

The data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.

Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy

A WW strategy for select rectal cancer patients who had a clinical complete response after neoadjuvant therapy resulted in excellent rectal preservation and pelvic tumor control; however, in the WW group, worse survival was noted along with a higher incidence of distant progression in patients with local reg growth vs those without local regrowth.

Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy: Long-term Results

Stage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy and Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.

Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer: a multicenter, randomized, non-comparative, phase II study (Oncodistinct 004 - AURA trial)

Oncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC.

Neoadjuvant Immune Checkpoint Blockade in High-Risk Resectable Melanoma

The feasibility of neoadjuvant immune checkpoint blockade in melanoma is described and the need for additional studies to optimize treatment regimens and to validate putative biomarkers is emphasized.

Pathological response and survival with neoadjuvant therapy in melanoma: a pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).

In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen, and, at this writing, no patient has died from melanoma.

Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer with Digital Rectal Examination, Endoscopy, and MRI: Selection for Organ-Saving Treatment

Clinical assessment afterCRT is the single most accurate modality for identification of CR after CRT, and addition of MRI with DWI further improves the diagnostic performance, and the combination can be recommended as the optimal strategy for a safe and accurate selection of CRafter CRT.