What is dostarlimab-gxly?
Dostarlimab is an anti-PD-1 humanized IgG4 monoclonal antibody. It inhibits programmed cell death 1 (PD-1) activity through binding to the PD-1 receptor located on T cells to block PD-L1 and PD-L2 ligands from binding. Blocking the PD-1 pathway leads to negative immune regulation caused by PD-1 receptor signaling.
Dostarlimab is initially FDA-approved for patients with advanced or recurrent solid tumors with the presence of deficient mismatch repair (dMMR) that have progressed on or following prior treatment, and who have no satisfactory alternative treatment options. Dostarlimab obtained an additional FDA approval for recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen and has the presence of dMMR, detected by an FDA-approved test.
Dostarlimab was approved with accelerated approval in solid tumors with dMMR based on the results of the GARNET trial-specifically cohort F. This trial was a non-randomized, multicenter, open-label, multi-cohort trial. Patients received dostarlimab 500 mg intravenously every 3 weeks for 4 doses, followed by 1,000 mg every 6 weeks until disease progression. Cohort F enrolled patients with dMMR or POLEmut non-endometrial solid tumors with 99 of the 106 patients having gastrointestinal tumors. The primary efficacy endpoints included overall response rate (ORR) and duration of response (DOR). The confirmed ORR was 38.7 percent with a complete response rate of 7.5 percent. The median DOR was not reached (J Clin Oncol 2021; doi: 10.1200/JCO.2021.39.3_suppl.9).
Cohort A1 in the GARNET trial evaluated dostarlimab for patients with dMMR recurrent or advanced endometrial cancer who progressed on or after platinum-containing treatment. They enrolled 71 patients with advanced endometrial cancer with dMMR. The confirmed ORR was 42.3 percent with a complete response rate of 12.7 percent and a partial response rate of 29.6 percent. The observed median DOR was not reached (JAMA Oncol 2020;6(11):1766-1772).
How do you administer dostarlimab-gxly?
Dostarlimab is infused intravenously over 30 minutes. It is administered as a 500 mg dose every 3 weeks for the first 4 doses, followed by 1,000 mg every 6 weeks.
Are there any pre-medications needed?
Dostarlimab has a minimal emetic risk. No routine pre-medications are recommended.
What are the common side effects?
The following side effects are reported for dostarlimab:
* Gastrointestinal: constipation (16-20%), decreased appetite (12-14%), diarrhea (25-26%), nausea (22-30%), vomiting (17-18%)
* Dermatologic: pruritus (15%), skin rash (14%)
* Increased lab values: aspartate aminotransferase (16-26%), alanine aminotransferase (15-22%), alkaline phosphatase (25-26%), serum creatinine (21-27%), calcium (6-15%), potassium (14%)
* Genitourinary: urinary tract infection (13%)
* Neuromuscular & Skeletal: asthenia (
* Hematologic: lymphocytopenia (33-37%), anemia (24-30%), decreased neutrophils (12%), leukopenia (18-21%)
* Respiratory: cough (13-14%)
* Decreased lab values: albumin (26-30%), magnesium (16%), potassium (14-15%), sodium (21-26%)
* Other: fatigue (
What are the uncommon side effects?
Sepsis, erythema of skin, pemphigoid, severe abdominal pain, pancreatitis, iridocyclitis, uveitis, acute kidney injury, interstitial nephritis, pneumonitis, infusion-related reaction, and immune-mediated toxicities.
What serious warning and precautions exist for dostarlimab-gxly?
The risk of immune-mediated toxicities exists with dostarlimab. These can include pneumonitis, colitis, hepatitis, and multiple endocrinopathies.
Are there any important drug interactions?
Coadministration with corticosteroids may diminish therapeutic effects of immune checkpoint inhibitors.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
No dose adjustments are provided for mild or moderate renal or hepatic dysfunction prior to treatment initiation. Patients experiencing renal or hepatic toxicity during treatment should be assessed for immune-mediated toxicities and managed as indicated per guidelines.
What should my patients know about dostarlimab-gxly?
* The Ventana MMR RxDx Panel was simultaneously approved as a companion diagnostic device to select patients with dMMR solid tumors for dostarlimab treatment.
* Pregnancy should be avoided due to the risk for embryo-fetal toxicity and both men and women should use effective contraception during treatment and at least 4 months following the last dose.
* Breastfeeding should be avoided during treatment and at least 4 months after the last dose.
What else should I know about this drug?
Immune-mediated toxicities can occur while on therapy and warrant early intervention with steroids and holding therapy based on degree of toxicity. Patients should be educated on toxicities such as adrenal insufficiency, hypophysitis, thyroid disorders, diabetes mellitus, diarrhea/colitis, myocarditis, pneumonitis, rash/dermatologic toxicity, neurotoxicity, and ocular disorders.
What useful links are available?
* FDA Approval: https://bit.ly/3AZlbLs
* Prescribing Information: https://bit.ly/3RqWAog
Any ongoing clinical trials?
Dostarlimab is also being studied in clinical trials of various phases and combinations in patients with advanced cancers. More information is available about these trials at http://clinicaltrials.gov.
SASHA HAARBERG, PHARMD, BCOP, is Clinical Oncology Pharmacist at the Siteman Cancer Center and Washington University School of Medicine, St. Louis, Mo. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.