Below are some highlights of the research presented at the 2022 meeting of the American Society of Clinical Oncology, which took place in Chicago, Illinois on June 3-7.
Much of the kidney cancer data presented during the 2022 meeting of the American Society of Clinical Oncology (ASCO) expanded upon previous work and clarified how to continue refining clinical trial design in order to generate meaningful, patient-driven outcomes, particularly in adjuvant therapy (medication given after surgery) and progression-free survival after second-line therapy (PFS-2).
“I was excited to see the adjuvant data for EVEREST,” said Dr. Chung-Han Lee of Memorial Sloan Kettering Cancer Center and a member of the Kidney Cancer Association’s Medical Steering Committee. “Technically, it’s a negative study but it does show how, for an adjuvant study, the population going into the study is incredibly important.”
In the phase III EVEREST trial, adjuvant treatment with the mTOR inhibitor everolimus led to a 21% reduced risk of disease recurrence or death compared with placebo in patients with high-risk RCC. Among all 1,499 people included in the trial, no matter their disease stage, there was an average 15% reduced risk of recurrence or death among those randomized to adjuvant everolimus, although this was slightly beyond the cutoff for statistical significance, unlike the high-risk group where there was a clear benefit.
“For a positive adjuvant study, you need to enroll people at high risk of having recurrent disease. And if you include people with lower risk, it dilutes the numbers. We probably did suspect this result from former adjuvant TKI data, but to see the same story play out again with an mTOR inhibitor was quite interesting,” Lee said. “In the end, we’re not using everolimus in the adjuvant setting, but it’s informative down the line when considering how we design clinical trials for adjuvant therapy in the future.”
Deb Maskens, a patient advocate, long-term metastatic cancer survivor, and member of the KCA’s Patient & Caregiver Advisory Council, spoke about the overwhelming unmet need for a better understanding of adjuvant therapy in RCC during a panel discussion on adjuvant therapy and value-based decision making.
“Patients want to live longer and better – there we agree,” she said. But, based on surveys from groups like the International Kidney Cancer Coalition and KCCure, uptake for adjuvant therapy in the targeted therapy era has been low due to side effects and lack of overall survival benefits. Patients also have a threshold of, for example, tolerable risk regarding the risk of cancer returning, a period of remaining cancer-free on scans, or the risk of side effects.
Moving forward, Maskens said, patients must be involved in the research process at every level from study design and analysis to publications so researchers can reach for meaningful, relevant endpoints. The ideal adjuvant therapy would allow for patient selection based on individual risk assessment, provide clear, relevant, meaningful benefits, minimize toxicity and long-term harm, and be affordable, accessible, and acceptable to patients and their families.
This year, Lee said, everyone seemed to be showing their PFS-2 data, with PFS-2 being the time from randomization to disease progression or death on a second-line of treatment. The trials with PFS-2 data to share included an expanded, 30-month follow-up analysis from the KEYNOTE-564 trial showing adjuvant pembrolizumab was superior to placebo after nephrectomy, the KEYNOTE-426 trial showing PFS-2 was longer with pembrolizumab plus axitinib versus sunitinib alone in advanced clear cell RCC even after 42 months, and the CLEAR study looking at lenvatinib plus pembrolizumab versus sunitinib in advanced RCC in which PFS-2 remained longer with the combination treatment.
“Real world data compares TKI/immunotherapy vs ipilimumab/nivolumab in real world with PFS as the endpoint. That’s the true treatment decisions we’re making right now,” Lee said. “What we learn from PFS-2 data echoes what we’ve seen before in terms of having TKIs still work after getting a TKI/immunotherapy regimen.”
August 2, 2022
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