Sapna P. Patel, MD, on Melanoma: New Data on Pembrolizumab, Adjuvant vs Neoadjuvant Plus Adjuvant
ESMO Congress 2022
Sapna P. Patel, MD, of The University of Texas MD Anderson Cancer Center, discusses the latest findings from the SWOG S1801 trial, which showed that using single-agent pembrolizumab as neoadjuvant therapy improved event-free survival compared to adjuvant therapy in high-risk resectable stage III–IV melanoma (Abstract LBA6).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The rationale behind neoadjuvant immunotherapy for melanoma is that cancer comes in contact with T cells that are inside the tumor. If you remove the tumor, you remove those T cells with it. On the other hand, if you give neoadjuvant therapy while the tumor is still in place and those T cells, you end up generating a larger immune response than if you give the same treatment after the tumor is removed. With that in mind, we designed the SWOG S1801 phase II trial. The study was a randomized one-to-one study for participants with stage IIIB to IV resectable melanoma. Participants on the adjuvant arm were randomized to surgery first followed by 18 doses of adjuvant pembrolizumab, flat-dosed every three weeks. Participants on the neoadjuvant arm received 3 doses of pembrolizumab followed by surgery, and then 15 doses of adjuvant pembrolizumab.
Neoadjuvant therapy with pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma. Toxicities were well-managed and no new safety signals emerged. In fact, the use of neoadjuvant pembrolizumab did not lead to an increase in surgery events. Compared to the same therapy given entirely after surgery, the use of neoadjuvant pembrolizumab improves event-free survival in patients with resectable melanoma. The next steps for S1801 include central pathologic review on the neoadjuvant specimens to determine a correlation between pathologic response and clinical outcomes. Future neoadjuvant studies can consider S1801 as a benchmark and expand on deescalation of surgery protocols, deescalation of adjuvant therapy, or escalation of neoadjuvant or adjuvant regimens for those whose tumors do not respond.
The ASCO Post Staff
Antonio Marra, MD, of Memorial Sloan Kettering Cancer Center, discusses a mutational signature analysis that reveals patterns of genomic instability linked to resistance to endocrine therapy with or without CDK4/6 inhibition in patients with estrogen receptor–positive/HER2-negative metastatic breast cancer (Abstract 210O).
The ASCO Post Staff
Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, and Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discuss results from two important trials presented at ESMO 2022: Cohort 1 of the LITESPARK-003 study of belzutifan plus cabozantinib as first-line treatment of advanced renal cell carcinoma (RCC), and the KEYNOTE-B61 study of pembrolizumab plus lenvatinib as first-line treatment for non–clear cell RCC (Abstracts 1447O and 1448O).
The ASCO Post Staff
Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, and Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discuss phase III findings showing that cabozantinib in combination with nivolumab and ipilimumab reduced the risk of disease progression or death compared with the combination of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma of IMDC (the International Metastatic RCC Database Consortium) intermediate or poor risk. However, the combination of cabozantinib, nivolumab, and ipilimumab vs nivolumab plus ipilimumab did not demonstrate an overall survival benefit to patients (Abstract LBA8).
The ASCO Post Staff
Bernd Kasper, MD, PhD, of Germany’s Mannheim Cancer Center, discusses phase III data from the DeFi trial, the largest study conducted to date for patients with desmoid tumors. The trial showed that the gamma secretase inhibitor nirogacestat demonstrated improvements in all primary and secondary efficacy endpoints. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and, occasionally, mortality in patients (Abstract LBA2).
The ASCO Post Staff
Myriam Chalabi, MD, PhD, of The Netherlands Cancer Institute, discusses data from the NICHE-2 study, which confirms previously reported pathologic responses to short-term neoadjuvant nivolumab plus ipilimumab in patients with locally advanced mismatch repair–deficient colon cancer. Survival data suggest neoadjuvant immunotherapy may become standard of care and allow further exploration of organ-sparing approaches. (Abstract LBA7).
