UPDATE: On March 10, 2023, Merck announced through a press release that its Phase 3 study met its primary endpoint of overall survival which was significantly higher in patients treated with the combination of chemotherapy and immunotherapy. Data will be released at a later time.
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The chemotherapy regimen of Alimta/cisplatin has long been the standard of care for mesothelioma. In the last few years, the immunotherapy combination of nivolumab/ipilimumab (Opdivo/Yervoy) became the second ever treatment approval for mesothelioma. Although there is much reason to be hopeful about the possibility that standard chemotherapy plus immunotherapy together provide a bigger survival benefit than each modality alone, clinical studies have not yet confirmed this. In fact, several studies investigating this combination are either ongoing or have not yet released their Phase 3 analyses.
This week, however, we got an additional glimpse into the potential benefit of this type of treatment with the release of the interim analysis covering only the Phase 2 component of the Phase 2/3 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma. The Phase 3 component of the study has fully accrued with results expected to be released later this year.
To best understand the results of this study it is important to first understand what a phase 2/3 trial is. In general, phase 2 clinical trials involve a larger number of participants compared to phase 1 trials and are designed to evaluate the safety and efficacy of the drug in a specific patient population. Phase 2 trials help determine the optimal dose and dosing schedule of the drug and can provide early evidence of its potential benefits.
Phase 3 trials, on the other hand, involve a larger number of patients and are designed to confirm the safety and effectiveness of the drug in a much larger patient population.
Therefore, a phase 2/3 clinical trial combines both of these phases into a single study. This approach can be more efficient, as it allows researchers to gather information on both the safety and efficacy of the drug in a relatively short amount of time. It can also help accelerate the drug development process, as promising drugs can move quickly from phase 2 to phase 3 trials without the need for additional studies.
The study, led by the Canadian Cancer Trials Group, in conjunction with the Italian National Cancer Institute and the French Cooperative Thoracic Intergroup randomized a total of 80 patients into three comparison groups (called arms of the study). Patients in this study were previously untreated and had advanced disease.
Arm 1: standard chemotherapy (Alimta/cisplatin)
Arm 2: standard chemotherapy (Alimta/cisplatin) + immunotherapy (Keytruda)
Arm 3: immunotherapy (Keytruda)
As far as safety was concerned, the authors concluded that standard chemotherapy plus immunotherapy was tolerable.
From the efficacy standpoint, the study investigators’ primary focus was the evaluation of progression-free-survival (PFS), a term used in clinical trials to measure the length of time during and after treatment that a patient lives without the disease getting worse. In this study, the PFS did not show much difference between Arm 1 and 2. However, even though overall survival (OS) was not part of the phase 2 study design, it appeared to benefit the participants in Arm 2 who received both chemotherapy and immunotherapy. But to know that with more certainty, we will need to wait for the phase 3 study results to be released.
If you have any questions about mesothelioma treatment or clinical trials, please contact our on-staff nurse for guidance.
