The US Food and Drug Administration has officially approved Merck’s KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with pemetrexed and platinum chemotherapy. This it did for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).
To give you some context, malignant mesothelioma is a type of cancer that starts in the linings of certain parts of the body, including the chest, abdomen, heart and testicles. From a worldwide standpoint, the healthcare industry witnessed more than 30,000 new cases of mesothelioma diagnosed, and more than 25,000 deaths from the disease in 2022. More on the same would reveal how peural mesothelioma is the most common form of malignant mesothelioma, accounting for about 75% of all cases. Making the approval in question even more important is a fact that the disease can progress rapidly, with the five-year survival rate for all stages for cases diagnosed across US, from 2014-2020, being 12.8%.
In response, Merck has introduced its KEYTRUDA therapeutic, which happens to be an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Furthermore, it is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thus activating T lymphocytes which may affect both tumor cells and healthy cells
“We’re pleased to offer a new first-line treatment option for adult patients with unresectable advanced or metastatic malignant pleural mesothelioma, a disease where prognoses are generally poor,” said Dr. Gregory Lubiniecki, vice president of oncology clinical research at Merck Research Laboratories. “This milestone underscores our commitment to advancing research for patients with difficult-to-treat tumors.”
Markedly enough, FDA’s approval of KEYTRUDA comes after a pivotal Phase 2/3 IND.227/KEYNOTE-483 trial, which is a multicenter, randomized, open-label, active-controlled Phase 2/3 trial sponsored and conducted by CCTG in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). Going by the available details, this particular study showed a statistically significant improvement in overall survival (OS), reducing the risk of death by 21%, as compared to chemotherapy alone at the trial’s pre-specified final analysis. Beyond that, median OS was 17.3 months (95% CI, 14.4-21.3) for KEYTRUDA plus chemotherapy versus 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. Moving on, KEYTRUDA plus chemotherapy also significantly improved progression-free survival (PFS) versus chemotherapy alone. As for the overall response date, it was significantly higher for KEYTRUDA plus chemotherapy versus chemotherapy alone.
The Phase 3 component of the trial enrolled 440 patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease, regardless of tumor PD-L1 expression.
Among other things, we must mention that patients who participated in the trial were randomized (1:1). Apart from that, all study medications were administered via intravenous infusion i.e. KEYTRUDA with pemetrexed and cisplatin, or carboplatin on Day 1 of each 21-day cycle for up to six cycles. This was followed up by KEYTRUDA every three weeks [Q3W]. The therapeutic was notably administered prior to chemotherapy on Day 1. Another intravenous infusion witnessed during the trial was pemetrexed and cisplatin or carboplatin on Day 1 of each 21-day cycle for up to six cycles.
Other relevant details include how treatment with KEYTRUDA continued until disease progression as determined by the investigator according to modified RECIST 1.1 for mesothelioma (mRECIST), unacceptable toxicity, or a maximum of 24 months. Talk about the assessment of tumor, it was performed every six weeks for 18 weeks, followed by every 12 weeks from there onwards.
