Investigators have demonstrated the promising activity of avelumab in a phase 2 study of patients with mismatch repair–deficient (MMRD) endometrial cancer, regardless of their PD-L1 status (J Clin Oncol. 2019 Aug 28. Epub ahead of print).

“Despite the tissue-agnostic approval of pembrolizumab in…[patients with MMRD]…solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair–proficient (MMRP) and –deficient endometrial cancer,” explained Panagiotis A. Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

Therefore, Dr Konstantinopoulos et al conducted a trial of avelumab in patients with MMRD/POLE (polymerase ε) endometrial cancer (ie, immunohistochemical (IHC) loss of MMR protein expression and/or documented mutations in the exonuclease domain of POLE or with MMRP endometrial cancer (ie, normal IHC expression of all MMR proteins). All patients were given avelumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity occurred.

The co-primary end points of the study were objective response (OR) and progression-free survival (PFS) at 6 months.

Among the 33 participants, no patients in the MMRD cohort (n = 17) had a POLE-mutated tumor, and all MMRP tumors were not POLE-mutated. The MMRP cohort (n = 16) was closed at the first stage due to futility (only 1 patient had OR and 6-month PFS responses).

Patients in the MMRD cohort met the predefined primary end point of 4 ORs; of 15 patients given avelumab, 4 exhibited OR (including 1 complete response and 3 partial responses; OR rate, 26.7%; 95% CI, 7.8%-55.1%) and 6 yielded 6-month PFS responses (PFS6, 40.0%; 95% CI, 16.3%-66.7%). Notably, 4 of the 6-month PFS responses are still ongoing.

According to the investigators, responses were observed even without PD-L1 expression, and IHC captured all subsequent MMRD cases determined by polymerase chain reaction or targeted sequencing.

“Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection,” Dr Konstantinopoulos said.

“The activity of avelumab in MMRP/non-POLE–mutated ECs was low,” they concluded.—Hina Porcelli