August 2023: Dostarlimab-gxly (Jemperli, GlaxoSmithKline), followed by dostarlimab-gxly as a single agent, was approved by the Food and Drug Administration for the treatment of primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).
RUBY (NCT03981796), en randomisert, multisenter, dobbeltblind, placebokontrollert studie, vurdert effekt. En forhåndsbestemt undergruppe på 122 pasienter med primær avansert eller tilbakevendende dMMR/MSI-H EC gjennomgikk en vurdering av effekt. Når lokale data ikke var tilgjengelige, ble sentral testing (IHC) ved bruk av Ventana MMR RxDx-panelet brukt til å vurdere MMR/MSI-svulststatus.
Patients were randomly assigned (1:1) to receive either placebo with carboplatin and paclitaxel, followed by placebo, or dostarlimab-gxly with carboplatin and paclitaxel, followed by dostarlimab-gxly. The aforementioned link provides detailed prescribing information on several chemotherapy regimens. MMR/MSI status, past external pelvic irradiation, and disease stage (recurrent, primary Stage III, or primary Stage IV) were all taken into account when stratifying the randomization process.
Investigator-assessed progression-free survival (PFS) using RECIST v. 1.1 was the main efficacy outcome measure. With a median PFS of 30.3 versus 7.7 months (Hazard Ratio=0.29 [95% CI: 0.17, 0.50]; p-value0.0001) for the dostarlimab-gxly and placebo-containing regimens, respectively, a statistically significant PFS improvement was seen in the dMMR/MSI-H group.
Pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal failure, and skin adverse responses are examples of immune-mediated adverse reactions that can occur with dostarlimab-gxly. Rash, diarrhoea, hypothyroidism, and hypertension were the most frequent adverse events (20%) with dostarlimab-gxly in combination with carboplatin and paclitaxel. For a complete list of side effects, refer to the prescribed information.
Dostarlimab-gxly skal administreres i en dose på 500 mg hver tredje uke i seks doser med karboplatin og paklitaksel, deretter 1,000 mg en gang hver sjette uke inntil sykdommen utvikler seg eller det er utålelig toksisitet, som kan ta opptil tre år. Når det gis samme dag som kjemoterapi, bør dostarlimab-gxly gis først.
Se full forskrivningsinformasjon for Jemperli.
