This week, Nature Medicine published the results, as well the genomic and immunologic analyses, from the Phase 2 PrE0505 clinical trial. The trial, which took place between 2017 and 2018, sought to investigate safety and efficacy signals of combination standard chemotherapy with added immunotherapy in previously untreated patients who are not surgical candidates.
(Patients and their families must be careful when interpreting statistical data. Comparing data between clinical studies is not advised due to study design differences. For help interpreting studies and determining the right treatment option for you, please contact the Mesothelioma Applied Research Foundation at (703) 879-3821 or speak with your physician).
The PrE0505 study showed a significantly higher overall median survival of 20.4 months as compared to historical data from the Alimta/cisplatin study which reported a median overall survival rate of 12.1 months. The objective response rate was 56.4%, meaning that over half of enrolled patients responded to this type of treatment. The study reported that 4 patients out of 55 discontinued treatment due adverse events. Overall, the addition of durvalumab immunotherapy led to few immune-related side effects grade 2 or lower. Overall, side-effects were consistent with those observed in patients undergoing chemotherapy treatment (such as anemia and fatigue).
The study emphasized that histology plays a significant role in both survival and response rate (epithelioid mesothelioma patients responded better than those with biphasic or sarcomatoid types, with overall survival in the epithelioid group beyond 2 years).
Within the context of the study, investigators also analyzed genomic and immunologic factors within the tumor to help them better understand underlying drivers of response.
“We are at a point in mesothelioma treatment research where we know that what works very well for some patients may not work at all for others,” said Shannon Sinclair, RN, BSN, OCN, the patient services director at the Mesothelioma Applied Research Foundation.
“Understanding which patients benefit from which treatment and why will be a crucial next step in mesothelioma research,” she added.
A new Phase 3 randomized controlled trial of the same agents is currently available to previously untreated, unresectable (not surgical candidates) patients in the United States and Australia. Just like its preceding Phase 2 trial, this one combines standard chemotherapy of pemetrexed (Alimta) and ciplatin (or another platinum-based chemo) with durvalumab. Durvalumab, also known by the brand name Imfinzi, which is a PD-L1 checkpoint inhibitor.
The new paradigm of combining chemotherapy with immunotherapy could be misunderstood as an effort to “throw the kitchen sink” at the cancer, but it is based on science that shows chemotherapy to have an immunogenic effect. What this means in simple terms is that when tumor cells are treated with chemotherapy, they release certain immune targets that can then be seen and attacked by the immune system, particularly when that immune system is given a boost by immunotherapy. This is why the combination of the two therapies has shown better results than the combined results of the two therapies administered separately.
