Merck...announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with...advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated...as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Pembrolizumab is recommended as an option for treating tumours with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency in adults with...advanced or recurrent endometrial cancer that has progressed during or after a platinum-based therapy, who cannot have curative surgery or radiotherapy

For recurrent endometrial cancer, NCCN recommends MSI-H or dMMR testing if not previously done. Pembrolizumab is indicated for patients with MSI-H or dMMR tumors that have progressed following prior treatment.

...- Prior to Cycle 1 Day 1 (C1D1), documentation of tumor dMMR/MSI-H status must be available based on local testing....

...- Patients must have deficient mismatch repair as demonstrated by lack of expression of at least one mismatch repair protein by immunohistochemistry (IHC) and/or evidence of microsatellite instability (MSI) high....

...- Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2)....

...- Any advanced solid tumor, with the exception of colorectal carcinoma (CRC), which is Microsatellite Instability (MSI)-High (MSI-H) OR...

...7 patients with pretreated advanced MSI-H/dMMR EC were enrolled (3 patients received pembrolizumab as first line treatment, 2 as second line, 1 as third line and 1 as fourth line)….4 patients achieved complete response (CR) as best treatment response, 1 partial response (PR), 1 stable disease (SD) and one had progressive disease (PD), with an overall ORR of 71%. The median PFS was 23 months.

This is a single center, retrospective study of patients with MMR deficiency EC who received ICI…. ICI with nivolumab or pembrolizumab showed a high ORR and durable response in our patients. It is imperative that we check every advanced EC for MMR deficiency, as this patient population has the potential to become long term survivors.

The objective of this study was to assess clinical outcomes and treatment patterns among MSI-H/dMMR aEC patients...Most patients (n = 92) received pembrolizumab; among these patients, rwPFS and OS were 29.0 months (95% CI: 18.0-NE) and 30 months (95% CI: 30.0-NA), respectively....Real-world evidence suggests that pembrolizumab monotherapy provides considerable clinical benefits and has become the standard of care for MSI-H/dMMR aEC patients...

These updated results reconfirm the robust and durable antitumor activity of pembro and show encouraging survival outcomes in patients with advanced endometrial carcinoma that is MSI-H/dMMR, who have PD following prior systemic therapy and are not candidates for curative surgery or radiation, supporting the use of pembro in this setting.

Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%)...ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cutoff date) was 30.8% (95% CI, 25.8‒36.2). Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months). Median progression-free survival was 3.5 months (95% CI, 2.3‒4.2 months) and median overall survival was 20.1 months (95% CI, 14.1‒27.1 months)...Pembrolizumab demonstrated clinically meaningful and durable benefit, with high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.

...Merck...today announced the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of the following microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer who have disease progression on or following at least one prior therapy....The CHMP’s recommendation was based on results from the Phase 2 KEYNOTE-158 trial as well as results from the Phase 2 KEYNOTE-164 trial...

The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months….Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.

Patients with measurable MSI-H/dMMR EC confirmed by polymerase chain reaction/immunohistochemistry were evaluated by WES and received 200 mg of pembrolizumab….The ORR was 100% in Lynch/Lynch-like patients but only 44% in sporadic patients (P = .024). The 3-year PFS and OS proportions were 100% versus 30% (P = .017) and 100% versus 43% (P = .043), respectively....This study suggests prognostic significance of Lynch-like cancers versus sporadic MSI-H/dMMR ECs for ORR, PFS, and OS when patients are treated with pembrolizumab.

ORR was 48%, with DOR ≥3 y in 68%....Pembro demonstrated robust and durable ORR (48%; CR, 14%), encouraging survival outcomes and manageable toxicity in pts with heavily pretreated, advanced MSI-H/dMMR EC, and is a promising treatment option in this setting.

Subjects with survivin-expressing advanced, recurrent HCC, NSCLC, bladder and MSI-H tumors are enrolled to single arm...DPXSurvivac/CPA with pembrolizumab is well tolerated and shows early signs of clinical efficacy and disease control in advanced and metastatic solid tumors...

129 MSI-H pts across 33 tumor types received first P after May 2017. CRC (N=36) and Endometrial cancer (N=39) were most common....P use was observed across 33 MSI-H tumor types. Median OS exceeded 1 yr across all pts and in CRC, Endometrial, and Other cohorts. 1 yr OS rate was consistent with P trial outcomes.

Our study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Median progression-free survival and median overall survival for the seven largest tumor cohorts are summarized in Table 3.

Here, we report a 62-year-old lady with metastatic endometrial cancer...she was started on chemotherapy with paclitaxel and carboplatin...paraffin-embedded tissue showed microsatellite instability (MSI-high [MSI-H])...As of now, she received a total of nine doses of pembrolizumab 200 mg once every 3 weeks...As the size of the primary lesion was remaining stable, and the sites of metastasis had responded well...