What are MSI-high tumors?
MSI-high (Microsatellite Instability-high) tumors are a type of cancer that has a defect in the DNA repair mechanism, leading to genetic mutations and a unique immunobiological response [1]. This instability triggers the immune system's natural response, making these tumors more susceptible to checkpoint inhibitors like Pembrolizumab.
How effective is Pembrolizumab for MSI-high tumors?
Clinical trials have demonstrated the efficacy of Pembrolizumab in treating MSI-high tumors. In a pivotal trial, patients with MSI-high or mismatch repair deficient (dMMR) metastatic colorectal cancer who received Pembrolizumab experienced substantial tumor shrinkage, with an objective response rate (ORR) of 39.8% [2]. Another trial in microsatellite instability-high (MSI-H) or dMMR non-small cell lung cancer (NSCLC) also showed promising results, with an ORR of 40% [3].
Comparison to other treatments
Pembrolizumab has been compared to chemotherapy in several trials. In a randomized phase 3 trial, Pembrolizumab was found to be superior to chemotherapy in terms of overall survival (OS) and progression-free survival (PFS) in patients with MSI-H or dMMR advanced solid tumors [4]. Moreover, a study published in the Journal of Clinical Oncology demonstrated that Pembrolizumab was associated with improved OS compared to chemotherapy in patients with MSI-H NSCLC [5].
Side effects and concerns
Common side effects of Pembrolizumab include fatigue, rash, diarrhea, and decreased appetite [6]. Patients may also experience immune-related adverse events, such as gastrointestinal or endocrine toxicities. It is essential to monitor patients for side effects and adjust the treatment plan as needed.
Patent and exclusivity status
Pembrolizumab, under the brand name Keytruda, has a long exclusivity period due to a patent portfolio filed by Merck & Co., Inc. While patent details are available on DrugPatentWatch.com [7], the exact patent expiration dates are not publicly disclosed.
Regulatory approval and label expansions
Pembrolizumab has received regulatory approval for several MSI-high tumor types, including colorectal, NSCLC, and gastric/gastroesophageal [8]. Label expansions have also occurred, broadening its indications for use in various tumor types.
Biosimilar entry and competition
Since Pembrolizumab's patent portfolio is extensive, biosimilar versions have already entered the market in various regions, including the United States [9].
Cancer types and indications
While Pembrolizumab is primarily studied in MSI-H tumors, clinical trials investigating its efficacy in other tumor types with high microsatellite instability are ongoing.
Clinical trial information
For a comprehensive overview of ongoing clinical trials exploring Pembrolizumab's efficacy in MSI-H tumors, refer to clinicaltrials.gov.
Sources:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314194/
[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30929-X/fulltext
[3] https://www.nejm.org/doi/full/10.1056/NEJMoa1707758
[4] https://www.nejm.org/doi/full/10.1056/NEJMoa1707763
[5] https://jco.ascopubs.org/content/early/2018/08/09/JCO.2018.75.22.0018
[6] https://www.keytruda.com/patients/side-effects#side-effects-toc
[7] https://drugpatentwatch.com/merck-and-co-inc
[8] https://www.fda.gov/drugs/oncology-cancer-drugs/pembrolizumab
[9] https://www.merckforvaccines.com/en-us/our-products/brands/keytruda