A brave new framework for glioma drug development.
Abstract Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential [...]
Two decades of advances in clinical oncology – lessons learned and future directions.
Abstract Since the publication of the first issue of Nature Reviews Clinical Oncology, we have witnessed advances in multiple research areas that have culminated in improved outcomes for many cancer types, although substantial unmet needs remain for a majority of patients worldwide. Here, we have asked experts in several key specialities to reflect on the progress from the past 20 years and propose the next steps to enable further advances. Although we are aware that this Viewpoint cannot provide full coverage of the vast field that is clinical oncology, we hope that these messages inspire a diverse range of readers. [...]
Nature and management of melanoma recurrences following adjuvant anti-PD-1 based therapy
Abstract Introduction: Approximately 50 % of resected stage II-IV melanoma patients develop recurrent disease by 5 years despite adjuvant anti-PD-1 therapy. Data to define best management of recurrences is lacking. Methods: This was a multicentre, international, retrospective cohort study. Patients with resected stage II-IV melanoma who commenced adjuvant anti-PD-1-based therapy before January 2022 and later recurred were identified. Data on demographics, disease characteristics, recurrence patterns, management and outcomes were collected. Results: 711 patients from 17 sites were included. Median age was 60 [range 16-92], 64 % were male, 2 % stage II, 91 % were stage III, 7 % stage IV. Median [...]
1090P High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma
Background The interferon gamma gene signature (IFNg) has been shown to be predictive and prognostic in patients (pts) with macroscopic stage III or IV melanoma. In macroscopic stage III melanoma, IFNg from lymph node biopsies (LN-IFNg) might be used in the future for neoadjuvant treatment decisions (combination vs monotherapy). To address the question of whether the IFNg can be analyzed using primary tumor material (P-IFNg) instead of LN-IFNg or, in the case of incongruencies, has a higher predictive value when combined with LN-IFNg, we analyzed the IFNg signature in paired samples (P and LN) from stage III melanoma pts. [...]
1082O KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma
Background Substudy 02C of the phase 1/2 KEYMAKER-U02 trial (NCT04303169) is evaluating neoadjuvant pembro with or without investigational agents followed by adjuvant pembro for stage IIIB-D melanoma. We present initial results from arm 4 (pembro + MK-4830 [anti-ILT4]) and arm 5 (favezelimab [anti-LAG-3] coformulated with pembro [fave/pembro]) and updated results from arm 1 (pembro + vibostolimab [vibo; anti-TIGIT]), arm 2 (pembro + gebasaxturev [geba; coxsackievirus A21]), and arm 3 (pembro alone). Methods Adults with resectable stage IIIB-D melanoma were randomly assigned to open arms. Patients (pts) received 2 doses of pembro 200 mg Q3W + vibo 200 mg Q3W [...]
1092P Nivolumab plus relatlimab vs nivolumab in previously untreated metastatic or unresectable melanoma: 3-year subgroup analyses from RELATIVITY-047
Background RELATIVITY-047 demonstrated a statistically significant improvement with nivolumab (NIVO) + relatlimab (RELA) vs NIVO for the primary endpoint of PFS per BICR. At the 3-y follow-up, NIVO + RELA continued to show clinically meaningful benefit vs NIVO for PFS, OS, and ORR per BICR in patients (pts) with previously untreated metastatic or unresectable melanoma. Here we report post hoc subgroup analyses with ∼3 y follow-up. Methods Pts were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg as a fixed-dose combination or NIVO 480 mg intravenously Q4W. Descriptive post hoc analyses were performed according to baseline [...]
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) [...]
1083P KEYMAKER 02B: A randomized trial of pembrolizumab (pembro) alone or with investigational agents as first-line treatment for advanced melanoma
Background Substudy 02B of the phase 1/2 KEYMAKER umbrella trial (NCT04305054) is evaluating first-line pembro (anti–PD-1) alone or with investigational agents for advanced melanoma. We present results from patients (pts) treated with pembro + vibostolimab (vibo; anti-TIGIT; arm 1), pembro alone (arm 2), quavonlimab (qmab; anti–CTLA-4) coformulated with pembro (qmab/pembro; arm 3), and qmab/pembro + lenvatinib (len; multitargeted TKI; arm 4). Methods Pts were aged ≥18 y with previously untreated unresectable stage III or IV cutaneous melanoma who had measurable disease per RECIST v1.1 and an ECOG PS of 0 or 1, but no active brain metastases. Pts were [...]