Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study.
Abstract Background: Patients with melanoma brain metastases respond well to immunotherapy, but long-term comparative survival data are scarce. We aimed to assess the efficacy of ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases at 7 years. Methods: This open-label, randomised, phase 2 study was conducted at four sites (two research institute cancer centres and two university teaching hospitals) in Australia. Patients aged 18 years or older with active, immunotherapy-naive melanoma brain metastases and Eastern Cooperative Oncology Group performance status of 0-2 were eligible. Asymptomatic patients with no previous brain-directed therapy were randomly assigned (5:4) using the biased-coin [...]
Patient and Staff Experiences of Embedding Electronic Patient Reported Outcome Measures for Distress Screening and Quality of Life Assessment, Into Routine Melanoma Care: A Mixed-Methods Study
Abstract Objective: Patient reported outcome measures (PROMs) are commonly collected in melanoma research. However, they are not used to guide immediate clinical care in Australia. This study explored the views and experiences of patients with Stage III melanoma and clinic staff during implementation of an electronic Patient-Reported Outcome Measures in melanoma (ePROMs-MEL) pilot to assess distress and quality of life. Methods: A prospective mixed-methods study in specialist melanoma clinics in Sydney, Australia between May 2021 and February 2023. Forty-two post-ePROMs implementation surveys and 17 semi-structured interviews were undertaken among patients and staff (including oncologists, melanoma nurses and clinic managers). Survey responses [...]
Patient and Staff Experiences of Embedding Electronic Patient Reported Outcome Measures for Distress Screening and Quality of Life Assessment, Into Routine Melanoma Care: A Mixed-Methods Study.
Abstract Objective: Patient reported outcome measures (PROMs) are commonly collected in melanoma research. However, they are not used to guide immediate clinical care in Australia. This study explored the views and experiences of patients with Stage III melanoma and clinic staff during implementation of an electronic Patient-Reported Outcome Measures in melanoma (ePROMs-MEL) pilot to assess distress and quality of life. Methods: A prospective mixed-methods study in specialist melanoma clinics in Sydney, Australia between May 2021 and February 2023. Forty-two post-ePROMs implementation surveys and 17 semi-structured interviews were undertaken among patients and staff (including oncologists, melanoma nurses and clinic managers). Survey responses [...]
Nivolumab (NIVO) plus relatlimab (RELA) vs. NIVO in previously untreated, metastatic, or unresectable melanoma (RELATIVITY-047): 3- year overall survival (OS) and melanoma-specific survival (MSS) results.
Abstract Introduction: The fixed-dose combination (FDC) of NIVO + RELA demonstrated a statistically significant progression-free survival (PFS) benefit compared to NIVO monotherapy in the RELATIVITY-047 study ( NCT03470922 ), a non-statistically significant increase in OS, and a numerically higher objective response rate (ORR), leading to regulatory approval of the FDC of NIVO + RELA. Here, we present updated descriptive analyses after 3 years of follow-up. Materials and Methods: Patients (pts) were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg FDC or NIVO 480 mg monotherapy every 4 weeks. PFS per RECIST v1.1 was assessed by blinded independent central review (BICR); secondary endpoints included OS and ORR per BICR. [...]
121MO Anti-IL-8 (BMS-986253) in combination with nivolumab (NIVO) plus ipilimumab (IPI) in patients (pts) with advanced melanoma: Final analysis from the randomized part 2 of the phase I/II CA027-002 study.
Abstract Background: Elevated serum IL-8 is associated with increased tumour burden, immunotherapy resistance, and poor outcomes in many solid tumour types. Low IL-8 correlates with improved response to checkpoint inhibitors. Anti–IL-8 (BMS-986253) is a fully human IgG1κ mAb. Anti–IL-8 +/– NIVO demonstrated tolerability in pts with selected advanced cancers. Here, we report the final analysis from part 2 of CA027-002, a randomized phase 2 study of anti–IL-8 + NIVO + IPI vs placebo (PBO) + NIVO + IPI in pts with advanced melanoma resistant to PD-(L)1 blockade. Methods: Pts with unresectable, stage III/IV melanoma who had progressed on/after anti–PD-(L)1 [...]
Efficacy and safety of nivolumab + relatlimab (NIVO+RELA) versus nivolumab + ipilimuab (NIVO+IPI) in the first-line (1L) treatment of advanced melanoma: updated data from an indirect treatment comparison.
Abstract Introduction An indirect comparison between NIVO + RELA and NIVO + IPI, 2 approved immunotherapy combination treatment options for patients with advanced melanoma, was previously conducted using individual patient data from the pivotal RELATIVITY-047 (RELA-047; NIVO + RELA vs. NIVO) and CheckMate 067 (CM-067; NIVO + IPI or NIVO vs. IPI) clinical trials. Here, we present the results obtained from the updated 3-year data from the RELA-047 trial. Materials and methods Inverse probability of treatment weighting was used to adjust for imbalances between patient baseline characteristics across the 2 trials. Database freezes were selected to best align follow-up duration in RELA-047 (median 34 months) and CM-067 [...]
Nivolumab vs. Placebo in the Adjuvant Treatment of Patients with Stage IIB/C Melanoma: 3-Year Results of the CheckMate 76K (CM 76K) Study.
Abstract Introduction Patients (pts) with resected stage IIB/C melanoma have a high risk of recurrence, similar to that of pts with resected stage IIIB melanoma. The CM 76K trial ( NCT04099251 ) demonstrated a significant reduction in the risk of recurrence or death with nivolumab (NIVO) compared with placebo (PBO) in pts with stage IIB/C melanoma who underwent complete resection. Updated data with 3 years of follow-up are presented here. Materials and methods Pts aged ≥ 12 years without evidence of residual disease after resection were stratified according to T category and randomized 2:1 to receive NIVO IV 480 mg or PBO every 4 [...]
Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma
Abstract Purpose: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. Patients and methods: Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary [...]
Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.
Abstract Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies. Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide [...]
Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma.
Abstract Background: In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods: This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of [...]