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).
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.
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).
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Ignace Vergote, MD, PhD, of Belgium’s University Hospitals Leuven, discuss interim safety and efficacy results from a third dose-expansion cohort evaluating first-line tisotumab vedotin-tftv plus pembrolizumab in patients with recurrent or metastatic cervical cancer. Data on the combination showed durable antitumor activity with a manageable safety profile (Abstract 5507).
Nabil F. Saba, MD, of Winship Cancer Institute of Emory University, discusses new data from a trial of pembrolizumab and cabozantinib in patients with recurrent metastatic head and neck squamous cell carcinoma. The study met its primary endpoint of overall response rate. The regimen was well tolerated and exhibited encouraging clinical activity in this patient population (Abstract 6008).
Mairéad G. McNamara, PhD, MBBCh, of The Christie NHS Foundation Trust, discusses phase II findings of the NET-02 trial, which explored an unmet need in the second-line treatment of patients with progressive, poorly differentiated extrapulmonary neuroendocrine carcinoma. In the trial, the combination of liposomal irinotecan, fluorouracil, and folinic acid, but not docetaxel, met the primary endpoint of 6-month progression-free survival rate (Abstract 4005).
Maxwell Oluwole Akanbi, MD, PhD, of McLaren Regional Medical Center, discusses the study he conducted, using the SEER database, to evaluate the impact of lung cancer screening recommendations on low-dose CT scanning. The data suggest that guidelines from the U.S. Preventive Services Task Force led to a more rapid decline in the incidence of advanced disease in the United States, especially among minority populations (Abstract 10506).