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).
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.
Martin Reck, MD, PhD, of Germany’s Lung Clinic Grosshansdorf, details two trials that included patients with advanced non–small cell lung cancer: 3-year survival outcomes in the EMPOWER-Lung 1 study of continued cemiplimab-rwlc beyond disease progression with the addition of chemotherapy, and phase III results from the IFCT-1701 trial of nivolumab plus ipilimumab 6-month treatment vs treatment continuation (LBA54 and Abstract 972O).
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, discusses results from the CheckMate 915 trial, an analysis of the pretreatment circulating tumor DNA, along with other clinical and translational baseline factors, and their association with disease recurrence in patients with stage IIIB–D/IV melanoma treated with adjuvant immunotherapy (Abstract 788O).
Marinde J.G. Bond, PhD Candidate, of the University Medical Center, Utrecht, discusses phase III findings from the CAIRO5 study of the Dutch Colorectal Cancer Group, the first such trial in defined subgroups of patients with initially unresectable colorectal cancer liver metastases and left-sided and RAS/BRAF V600E wild-type tumor. The study compared FOLFOX/FOLFIRI plus either bevacizumab or panitumumab (Abstract LBA21).
Richard S. Finn, MD, of the Geffen School of Medicine at the University of California, Los Angeles, discusses primary phase III results from the LEAP-002 study of pembrolizumab, an anti–PD-1 therapy, plus lenvatinib, the orally available multiple receptor tyrosine kinase inhibitor, vs lenvatinib monotherapy in patients with advanced hepatocellular carcinoma (Abstract LBA34).
Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, and Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute, discuss two important phase III studies on renal cell cancer (RCC) presented at ESMO 2022: IMmotion010, which examined the efficacy and safety of atezolizumab vs placebo as adjuvant therapy in patients with RCC at increased risk of recurrence after nephrectomy; and CheckMate 914, which compared nivolumab monotherapy or nivolumab combined with ipilimumab vs placebo in patients with localized disease who underwent radical or partial nephrectomy and who are at high risk of relapse. (Abstract LBA4 & LBA66).