Neoadjuvant pembrolizumab plus lenvatinib in patients with resectable stage III melanoma (NeoPele): Analysis of tumor microenvironment (TME) correlated to pathological
Abstract Background: The phase II SWOG S1801 study showed an improved event-free survival with anti-PD-1 (PD1) neoadjuvant immunotherapy (neoIT) vs adjuvant PD1. One hypothesis explaining this benefit is the presence of tumor-draining lymph nodes (tdLN; defined as the nearest node to the tumor without direct involvement) as a potential reserve of stem-like (TCF7+) T cells, crucial to a good response to IT. We sought to analyze the immune infiltrate of the tumor-involved LN (ie TME) and tdLN from patients (pts) achieving major pathological response (MPR: complete [pCR] or near-complete [near-pCR] pathological response) vs non-MPR (partial [pPR] or no [pNR] [...]
LBA41 Long-term survival with neoadjuvant therapy in melanoma: Updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
Background Neoadjuvant therapy is the standard of care for resectable stage ≥IIIB melanoma. In 2021, the International Neoadjuvant Melanoma Consortium published a pooled analysis of 196 melanoma pts treated with neoadjuvant immunotherapy (ICI) or BRAF/MEK targeted therapy. Here, we provide a survival update of an expanded cohort. Methods Clinical, radiographic, histopathological, and survival data were collated for pts with resectable stage ≥IIIB melanoma who received neoadjuvant therapy in a clinical trial or routine care. Outcomes included major pathological response (MPR) rate, event-free survival (EFS; progression prior to surgery, recurrence post-surgery or death), and recurrence-free survival (RFS). Results Data was [...]
1106P NivoLag-when: International real-world study of combination immunotherapy sequences in melanoma
Background Three immune checkpoint inhibitor (ICI) regimens are standard of care in metastatic melanoma (MM): anti-PD1 combined with anti-CTLA4 (ipi/nivo), with anti-LAG3 (rela/nivo) or as monotherapy. Data describing the efficacy of sequential regimens are limited. Methods This multicenter retrospective and prospective study assessed patients (pts) who received rela/nivo followed by ipi/nivo (A); ipi/nivo followed by rela/nivo (B); or anti-PD1 followed by rela/nivo (C). Primary endpoint was objective response rate (ORR) to second treatment (Tx). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results With a median follow-up of 62.5 months (mo), 130 pts (A=26; B=43; C=61) [...]
1088P Molecular profiling and matched targeted therapy for patients with advanced melanoma: Results from part I of the MatchMEL study
Background While the molecular landscape of melanoma (Mel) has been defined, the clinicopathological associations of pts with BRAF/NRAS wild-type (WT) Mel and immune-checkpoint inhibitors (ICIs) treatment outcomes are less well understood. The MatchMEL study investigated the mutational profile of WT Mel and examined whether targeted treatments could be matched to specific molecular alterations with clinical efficacy. Methods In Part 1, consecutive pts with newly diagnosed advanced Mel presenting to two centres in Australia were enrolled. WT pts underwent FoundationOneCDx® (CDx) sequencing. Clinicopathologic features and ICI outcomes were examined. A molecular tumor board analysed CDx results to match targeted therapy [...]
Comparison of clinicopathological features and treatment outcomes for cutaneous melanomas of the head and neck and melanomas arising at other sites: Implications for systemic therapy.
Abstract Background: Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity. Objective: Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS). Methods: Patients with CHNM and CMOS diagnosed between 2000 and 2018 were included. Locoregional control, distant metastasis-free survival, melanoma-specific survival (MSS), and overall survival (OS) were described using the Kaplan-Meier method. Cox regression analyses were performed to examine associations between prognostic factors and outcomes. Additional analyses of survival from time of stage IV disease diagnosis were undertaken, stratified by receipt [...]
Exploiting temporal aspects of cancer immunotherapy
Abstract Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. To improve outcomes, a multitude of clinical trials are testing combinations of ICT with various other treatment modalities. Ideally, those combination treatments should take time-dependent immunological events into account. Recent studies have started to map the dynamic cellular [...]
Exploiting temporal aspects of cancer immunotherapy
Abstract Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. To improve outcomes, a multitude of clinical trials are testing combinations of ICT with various other treatment modalities. Ideally, those combination treatments should take time-dependent immunological events into account. Recent studies have started to map the dynamic cellular [...]
Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study.
Abstract Introduction: The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs. Methods: A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers. We sought to characterize the frequency and location of oligoprogression and determine the overall survival (OS) after radiotherapy in this population. Results: A total of 159 patients were included in the study. At [...]
Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases.
Abstract Background: The combination of anti-PD-1 and anti-CTLA-4 has been associated with improvement in response and survival over anti-PD-1 monotherapy in unselected patients with advanced melanoma. Whether patients with liver metastases also benefit from the combination of anti-PD-1 and anti-CTLA-4 over anti-PD-1, is unclear. In this study, we sought to assess whether the combination of anti-PD-1 and anti-CTLA-4 leads to better response, progression-free survival and overall survival, compared with anti-PD-1 monotherapy for patients with liver metastases. Methods: We have conducted an international multicentre retrospective study. Patients with advanced melanoma with liver metastases treated with 1st line anti-PD1 monotherapy or with [...]
Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases.
Abstract Background: The combination of anti-PD-1 and anti-CTLA-4 has been associated with improvement in response and survival over anti-PD-1 monotherapy in unselected patients with advanced melanoma. Whether patients with liver metastases also benefit from the combination of anti-PD-1 and anti-CTLA-4 over anti-PD-1, is unclear. In this study, we sought to assess whether the combination of anti-PD-1 and anti-CTLA-4 leads to better response, progression-free survival and overall survival, compared with anti-PD-1 monotherapy for patients with liver metastases. Methods: We have conducted an international multicentre retrospective study. Patients with advanced melanoma with liver metastases treated with 1st line anti-PD1 monotherapy or with anti-CTLA-4 [...]