The U.S. Food and Drug Administration granted accelerated approval on Monday for the PD-1 inhibitor dostarlimab (Jemperli) to treat certain operable rectal cancers.
Targeted patient group
The clearance applies to stage II or III rectal tumors that are mismatch-repair-deficient or microsatellite-instability-high (dMMR/MSI-H). This molecular profile represents roughly 3% of locally advanced cases and identifies a group whose cancers behave differently from most.
Current standard care combines chemotherapy, radiation and surgery.
Trial results and safety profile
Data from the AZUR-1 trial showed most participants with dMMR/MSI-H disease achieved a complete response, allowing them to forego the usual surgical approach.
Principal investigator Andrea Cercek, MD said neoadjuvant PD-1 inhibition could potentially eliminate the need for chemotherapy, radiation and surgery in about 2%–3% of all solid tumors.
The company that makes the drug noted the trial demonstrates a fundamentally different treatment path for this biomarker-defined population, giving patients access to a therapy matched to their tumor biology.
For those receiving the therapy, the shift means fewer invasive procedures, provided they undergo appropriate biomarker testing at diagnosis to confirm eligibility.
Michael Sapienza, chief executive of the Colorectal Cancer Alliance, said many facing rectal cancer worry about life after treatment, and the chance to avoid chemo, radiation and surgery is a meaningful advance for families.
Follow-up analysis revealed 76% of evaluable patients showed no cancer evidence after at least one year. After a median follow-up exceeding two years, no recurrences were reported among the study cohort.
The approval label states continued use depends on verification of clinical benefit in a confirmatory trial, as long-term relapse risk remains uncertain.
Adverse events were generally mild; fatigue occurred in 32% of patients, rash in 22%, diarrhea in 18% and itching in 17%. These side effects were typically manageable with standard supportive care.
Severe (grade 3) events each affected a single individual and included diabetes, lung infection, hypothyroidism, encephalitis and neutropenia. One case of grade 4 febrile neutropenia was also reported.
Prescribing information warns of a range of immune-mediated side effects that clinicians must monitor closely during treatment.
Beyond rectal cancer, the medication holds approvals for certain endometrial cancers and for previously treated dMMR recurrent or advanced solid tumors.
