Dostarlimab as Primary Treatment in MSI-High Solid-Tumor Cancers

Immune checkpoint inhibitors are highly effective treatment for DNA mismatch repair deficient (dMMR)/microsatellite instability (MSI)–high cancers. In a phase 2 trial of the PD-1 inhibitor dostarlimab, investigators reported a 100% rate of clinical complete response in 12 patients with MSI-high locally advanced rectal cancer, eliminating the need for chemotherapy, radiation, and surgery (NEJM JW Oncol Hematol Jun 29 2022 and N Engl J Med 2022; 386:2363). Now, they report findings in 49 patients with MSI-high rectal cancer and 54 patients with nonrectal MSI-high locally advanced solid tumors who completed 6-month treatment with dostarlimab.

In the rectal cancer cohort:

• All patients achieved a clinical complete response, and none received upfront surgery, chemotherapy, or radiotherapy.
• Recurrence-free survival at 2 years was 96%.

In the cohort with nonrectal cancers (including esophagogastric, colon, hepatobiliary, genitourinary and gynecologic cancers):

• 35 patients (65%) achieved a clinical complete response, 33 (61%) were placed on observation, and 2 who opted for surgery had pathologic complete responses.
• In the 19 patients not achieving clinical complete response, 3 who deferred surgery and 16 who underwent surgery all exhibited pathologic response.
• Recurrence-free survival at 2 years was 85%.

Among both cohorts:

• Only 5 patients developed recurrence — 4 in lymph nodes and 1 in the rectal primary.
• No patient had salvage surgery on the primary, 1 had salvage surgery of a lymph node, and 3 received retreatment with immunotherapy.
• No deaths occurred in either cohort.