Georgina V. Long, MD, PhD, on Melanoma: Distant Metastasis–Free Survival With Adjuvant Pembrolizumab
2022 ASCO Annual Meeting
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, The University of Sydney, discusses phase III findings from the KEYNOTE-716 study. The trial showed that compared with placebo, adjuvant pembrolizumab significantly improved distant metastasis–free survival in patients with resected stage IIB and IIC melanoma. The findings also suggest a continued reduction in the risk of recurrence and a favorable benefit-risk profile (Abstract LBA9500).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Keynote 716 is a phase three randomized trial of adjuvant pembrolizumab versus placebo in resected stage 2B and 2C melanoma. Historically from retrospective studies, stage 2B and C melanoma has been thought to be not as high risk as it actually is. In fact, many patients recur at 24 months and beyond, and these patients have very poor outcomes. So I'm reporting the distant metastasis free survival from this trial. We've previously reported on the relapse free survival on two previous analyses. And what we see is pembrolizumab significantly improves the distant metastasis free survival compared with placebo with a hazard ratio of 0.64, this represents a 36% reduction in the risk of recurrence, and a P value of 0.0029. This is highly significant. We also see on the 24 month and the 12 month landmark distant metastasis free survival rates, a significant increase compared with placebo of pembrolizumab. What's more in this study when we look at the subgroups, key subgroups, every subgroup favors pembrolizumab compared with placebo for the distant metastasis free survival, including the T subcategories 3B, 4A and 4B, as well as the US geographical region. We also see a sustained improvement in the relapse free survival. So at this analysis, this is the third analysis for the relapse free survival. It was the first for distant metastasis free survival. We see a hazard ratio of 0.64 and continued separation of the Kaplan-Meier curves for the relapse-free survival, meaning that adjuvant pembrolizumab significantly decreases the risk of recurrence for patients with resected stage 2B and 2C melanoma. So what are the next steps? The next steps are that we will continue to follow up with this trial and look at the overall survival benefit. In the design of this trial, we had crossover at recurrence. So patients were initially randomized to placebo versus pembrolizumab. But if they recurred, they were unblinded. If they were on the placebo arm or on the pembrolizumab arm, and they had their last dose of pembrolizumab six months or further prior, they were eligible to cross over to pembrolizumab. So we'll also be watching for the overall survival in the coming years. The take home message is that adjuvant pembrolizumab significantly improves both the relapse free survival and the distant metastasis free survival, and should be considered for patients with resected stage 2B and 2C melanoma.
The ASCO Post Staff
Manali I. Patel, MD, MPH, of Stanford University School of Medicine, discusses clinical trial findings on the best ways to integrate community-based interventions into cancer care delivery for low-income and minority populations. Such interventions may improve quality of life and patient activation (often defined as patients having the knowledge, skills, and confidence to manage their health), as well as reduce hospitalizations and the total costs of care (Abstract 6500).
The ASCO Post Staff
Pamela L. Kunz, MD, of the Yale University School of Medicine, discusses new findings from the ECOG-ACRIN E2211 trial, which showed the longest progression-free survival and highest response rates with temozolomide plus capecitabine reported to date for patients with pancreatic neuroendocrine tumors. The presence of a deficiency of MGMT, the drug-resistance gene, was associated with greater odds of an objective response (Abstract 4004).
The ASCO Post Staff
Andrew D. Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center, and Michael L. Wang, MD, of The University of Texas MD Anderson Cancer Center, discuss primary results from the phase III SHINE study, which showed that ibrutinib, in combination with bendamustine/rituximab and rituximab maintenance, may set a new benchmark for patients aged 65 or older with mantle cell lymphoma. With a median progression-free survival of 6.7 years, the ibrutinib combination is more beneficial than currently used chemoimmunotherapy (approximately 1.5–3.5 years) (Abstract LBA7502).
The ASCO Post Staff
Martin McCabe, PhD, of the University of Manchester, discusses a phase III assessment of chemotherapy for patients with recurrent and primary refractory Ewing sarcoma. The trial, called rEECur, is the first study to provide comparative toxicity and survival data for the four most commonly used chemotherapy regimens in this disease. The analysis showed that high-dose ifosfamide is more effective in prolonging survival than topotecan plus cyclophosphamide (Abstract LBA2).
Paul G. Richardson, MD, of Dana-Farber Cancer Institute, discusses phase III findings from the DETERMINATION trial, which showed that, for patients with newly diagnosed multiple myeloma, lenalidomide, bortezomib, and dexamethasone (RVd) with or without autologous stem cell transplant (ASCT) and lenalidomide maintenance to disease progression resulted in the longest median progression-free survival reported for each approach, and a highly significant difference in progression-free survival in favor of early transplant. While overall response rates were similar, rates of MRD favored early transplant also, but toxicity was greater and quality of life was transiently but significantly diminished. No overall survival advantage has been observed to date (Abstract LBA4).