Publications by authors named "Jean Jacques Grob"

Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.

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Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study.

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  • The study investigates the effects of continuing immune checkpoint inhibition (ICI) treatment in patients with metastatic melanoma who experience disease progression, using data from 120 patients.
  • It finds that patients who continued ICI treatment had a median overall survival (OS) of 4.2 months, significantly longer than the 1.3 months for those who stopped treatment after progression.
  • Despite the survival benefits, the study noted increased hospitalizations and treatments at the end of life in patients continuing ICI, highlighting the need for balanced palliative care.
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  • Nivolumab (NIVO) combined with ipilimumab (IPI) shows better long-term overall survival (OS) in patients with unresectable/metastatic melanoma than NIVO alone, based on pooled data from major trials.
  • Patients treated with the combination therapy had a median follow-up OS of 45.0 months, with 6-year survival rates at 52%, compared to 41% for NIVO monotherapy after a median follow-up of 35.8 months.
  • Clinical factors affecting survival include elevated lactate dehydrogenase (LDH) levels, age over 65 with the combination therapy, and presence of liver metastases with NIVO alone.
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  • A phase 3 trial found that 12 months of adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with high-risk stage III melanoma compared to placebo, with longer follow-up data available.
  • With a median follow-up of 6.9 years, the pembrolizumab group showed a 50% RFS at 7 years versus 36% for the placebo group, and a 54% DMFS compared to 42% in the placebo group.
  • The results indicated consistent positive outcomes across various melanoma subtypes, confirming the long-term benefits of pembrolizumab in improving survival metrics in these patients.
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  • - The phase 2 EMPOWER-CSCC-1 study showed that cemiplimab is effective against advanced cutaneous squamous cell carcinoma (CSCC), specifically in metastatic and locally advanced cases.
  • - The study involved different treatment groups receiving either weight-based or fixed-dose cemiplimab, with a significant overall response rate (ORR) of 47.2% after 42.5 months and noted long-duration responses.
  • - While the findings are promising, the study's limitations include its nonrandomized design and the fact that the primary endpoint was not based on survival rates.
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  • Nivolumab combined with relatlimab and ipilimumab has been approved for treating advanced melanoma based on clinical trials, but no direct comparison of the two treatments existed, leading to an indirect comparison using patient-level data.
  • The study utilized inverse probability of treatment weighting to balance patient characteristics and compared various outcomes like progression-free survival and treatment-related adverse events, finding both regimens had similar efficacy.
  • Nivolumab plus relatlimab showed a better safety profile, with fewer severe side effects and treatment discontinuations than nivolumab plus ipilimumab, although some subgroup analyses suggested varying results.
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Purpose: In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.

Patients And Methods: Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent.

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  • SAR439459 (SAR'459) is a new monoclonal antibody designed to improve the effects of immune checkpoint inhibitors, and it was tested for safety and effectiveness in patients with advanced solid tumors.* -
  • The study, which consisted of multiple phases, revealed that the maximum dose tolerated was never reached, but adverse effects included significant events such as hemorrhagic issues and skin neoplasms.* -
  • Ultimately, the combination therapy showed limited preliminary antitumor activity, which led to the decision to discontinue the study due to unclear effectiveness.*
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Background: Cutaneous adnexal carcinomas are a heterogeneous group of rare neoplasms. Surgical excision is the first-line treatment in localized stage. The use and effectiveness of radiotherapy have not been thoroughly evaluated in these neoplasms.

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Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.

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JCO Pembrolizumab adjuvant therapy was shown to significantly improve recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB or IIC melanoma in earlier analyses of the randomized, double-blind, phase III KEYNOTE-716 study (ClinicalTrials.gov identifier: NCT03553836). We report results of the protocol-specified final analysis of DMFS for KEYNOTE-716.

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Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial.

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What Is This Summary About?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells.

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  • * In the study, doctors tested different doses of SAR439459 and cemiplimab in patients with advanced cancer, focusing on people with melanoma, which is a type of skin cancer.
  • * The results showed that the medicine decreased levels of TGFβ in the body and changed how the immune system responds to tumors, but more research is needed to figure out how to tell which patients will benefit the most.
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BACKGROUND: A phase 2/3 trial — A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047) — evaluated nivolumab + relatlimab as a fixed-dose combination and found a significant progression-free survival (PFS) benefit over nivolumab monotherapy in previously untreated unresectable or metastatic melanoma. We now report updated PFS and safety data and the first results for overall survival (OS) and objective response rate (ORR). METHODS: Patients were randomly assigned 1:1 to receive nivolumab 480 mg and relatlimab 160 mg fixed-dose combination or nivolumab 480 mg alone, given intravenously every 4 weeks.

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Melanoma is still a major health problem worldwide. Early diagnosis is the first step toward reducing its mortality, but it remains a challenge even for experienced dermatologists. Although computer-aided systems have been developed to help diagnosis, the lack of insight into their predictions is still a significant limitation toward acceptance by the medical community.

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Introduction: At first interim analysis of KEYNOTE-629, health-related quality of life (HRQoL) with pembrolizumab was stable or improved over 48 weeks in recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). HRQoL results from the second interim analysis in R/M or locally advanced (LA) cSCC are presented.

Methods: Patients received pembrolizumab 200 mg every 3 weeks for ≤ 2 years.

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Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS).

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  • * Despite a good prognosis, cSCC leads to many deaths because of its high occurrence, highlighting the importance of ongoing research and treatment recommendations.
  • * A group of experts from various European dermatological and oncology organizations has come together to update guidelines on cSCC, focusing on various aspects such as classification, diagnosis, risk factors, and prevention for both immunocompetent and immunosuppressed individuals.
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  • A multidisciplinary panel of experts from various European medical organizations has developed updated recommendations for treating invasive cutaneous squamous cell carcinoma (cSCC) based on a thorough literature review and expert consensus.
  • Treatment guidelines cover different stages of cSCC, recommending surgery with clear margins as the primary option for low and high-risk cases, while highlighting the lack of benefit from radiation for high-risk patients with clear margins.
  • For advanced cSCC that cannot be surgically treated, anti-PD-1 agents like cemiplimab are recommended as first-line therapy, with second-line options including cetuximab combined with chemotherapy or radiation.
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Background: Sonidegib is approved to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiation. The BOLT trial demonstrated durable efficacy of sonidegib in laBCC patients over 42 months. BCC is most common in the elderly, who often take chronic medications.

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