Georgina V. Long, MD, PhD, on Resected Melanoma: Biomarkers for and Efficacy of Adjuvant Nivolumab vs Placebo
2023 ASCO Annual Meeting
Georgina V. Long, MD, PhD, of Melanoma Institute Australia and The University of Sydney, discusses new data showing that patients with resected stage IIB/C melanoma who were treated with adjuvant nivolumab had prolonged recurrence-free survival compared with placebo across all biomarker subgroups. The baseline biomarkers most predictive of prolonged recurrence-free survival with nivolumab were high interferon gamma score, high tumor mutational burden, CD8 T-cell infiltration, and low C-reactive protein (Abstract 9504).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Georgina V. Long:
Resected Stage 2B and 2C melanoma has a very poor prognosis. In fact, at five years, patients with stage 2C melanoma have a 45% risk of recurrence. And for stage 2B melanoma, 35% risk of recurrence. The survival of this group of patients is worse than that of stage 3A melanoma and the survival of stage 2C melanoma is equivalent to the survival of stage 3B melanoma. This is a poor prognostic group. Checkmate 76K explored adjuvant nivolumab versus placebo in resected stage 2B and 2C melanoma in patients who had undergone a wide local excision and a sentinel node biopsy, which was negative.
790 patients were randomized two to one to nivolumab versus placebo. We've already seen the relapse-free survival primary analysis last year, and there was a 58% reduction in the risk of recurrence with adjuvant nivolumab. We are now presenting the exploratory biomarker analysis from this trial. So baseline, primary melanoma tissue, and baseline CRP, serum CRP was correlated with outcome within each arm and versus each arm. And what we found was that for every biomarker subgroup, nivolumab improved the relapse-free survival over placebo.
And this included tumor mutation burden, interferon gamma, PD-L1 expression at baseline, CD8 infiltration at baseline, the CRP. So when we compared the prognostic biomarkers overall in the trial, we found that the two factors that were most important for prognosis, so predicting recurrence in the total trial population, that was the CRP and the stage. However, when we did our multivariate model to look at what was predictive of best outcome with adjuvant nivolumab over placebo, we found that the baseline biomarkers that were predictive or most predictive were the interferon gamma at baseline and the tumor mutation burden.
Our next steps are to make a multifactorial model, which includes both clinical and tissue biomarkers to predict outcome of patients with resected 2B and 2C melanoma treated with adjuvant nivolumab.
The ASCO Post Staff
Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Adnan Khattak, MBBS, FRACP, PhD, of Australia’s Hollywood Private Hospital & Edith Cowan University, discuss the use of the mRNA-4157 vaccine in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma, which prolonged distant metastasis–free survival compared with pembrolizumab alone. These results provide further evidence that a personalized neoantigen approach is potentially beneficial (Abstract LBA9503).
The ASCO Post Staff
Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Zeynep Eroglu, MD, of H. Lee Moffitt Cancer Center and Research Institute, discusses phase II findings showing that in patients with BRAF-mutant metastatic melanoma, dabrafenib plus trametinib and navitoclax (DTN) was associated with a complete response rate of 20% and an overall response rate of 84%. Additionally, there was a trend toward improved overall survival in patients treated with DTN compared with dabrafenib plus trametinib alone; the difference in overall survival was more pronounced in patients with a smaller tumor burden (Abstract 9511).
The ASCO Post Staff
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
The ASCO Post Staff
Thomas E. Hutson, DO, PharmD, of Texas Oncology, discusses the 4-year follow-up results from the CLEAR study for patients with advanced renal cell carcinoma (RCC). The data showed that lenvatinib plus pembrolizumab continues to demonstrate clinically meaningful benefit vs sunitinib in overall and progression-free survival, as well as in overall and complete response rates, in first-line treatment (Abstract 4502).
The ASCO Post Staff
Tycel J. Phillips, MD, of City of Hope National Medical Center, and Emanuele Zucca, MD, of the Oncology Institute of Southern Switzerland and the International Extranodal Lymphoma Study Group, discuss findings from the largest prospective study of patients with primary mediastinal B-cell lymphoma. The trial data support omitting radiotherapy in patients who achieve complete metabolic response after immunochemotherapy (Abstract LBA7505).
