Current status and perspectives in immunotherapy for metastatic melanoma

Marconcini, Riccardo; Spagnolo, Francesco; Stucci, Luigia Stefania; Ribero, Simone; Marra, Elena; Rosa, Francesco De; Picasso, Virginia; Guardo, Lorenza Di; Cimminiello, Carolina; Cavalieri, Stefano; Orgiano, L.; Tanda, Enrica T.; Spanó, Laura; Falcone, Alfredo; Queirolo, Paola; Palmieri, Giuseppe; Stanganelli, Ignazio; Mandalà, Mario; Quaglino, Pietro; Botti, Gerardo; Caracò, Corrado; Sileni, V. Chiarion; Giacomo, Anna Maria Di

doi:10.18632/oncotarget.23746

Cited by 78 publications

(75 citation statements)

References 119 publications

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“…Anti-CTLA4, widely studied for melanoma, acts to block the inhibitory signal involving the CTLA4 molecule between antigen-presenting cells and T lymphocytes. 2 Anti-PD1 compounds analogously block the inhibitory signal involving the PD1 receptor. 3 In both cases, diminishing tumormediated immune-attenuating effects results in more robust T-cell activation and immunemediated neoplastic destruction.…”

Section: Introductionmentioning

confidence: 99%

Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials

Chen

Menon

Verma

et al. 2020

J Immunother Cancer

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BackgroundThis study compared response rates and outcomes of combined radiotherapy and immunotherapy (iRT) based on the type of checkpoint inhibitor (anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) vs antiprogrammed death-1 (PD1)) for metastatic non-small cell lung cancer (mNSCLC).MethodsWe retrospectively reviewed two prospective trials of radiation combined with anti-CTLA4 or anti-PD1 for patients with mNSCLC. Patients undergoing non-salvage stereotactic body radiation therapy (SBRT) to lung sites were selected from both trials and grouped by the immunotherapeutic compound received. Endpoints included in-field and out-of-field response rates, and overall response rate (complete or partial response) (all by response evaluation criteria in solid tumors). Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method.ResultsMedian follow-up times for the 33 patients (n=17 SBRT+anti-CTLA4, n=16 SBRT+anti-PD1) were 19.6 and 19.9 months. Response rates for out-of-field lesions were similar between anti-PD1 (37%) and anti-CTLA4 (24%) (p=0.054). However, global response rates for all lesions were 24% anti-CTLA4 vs 56% anti-PD1 (p=0.194). The PFS was 76% for anti-CTLA4 vs 94% anti-PD1 at 3 months, 52% vs 87% at 6 months, 31% vs 80% at 12 months, and 23% vs 63% at 18 months (p=0.02). Respective OS values were 76% vs 87% at 6 months, 47% vs 80% at 12 months, and 39% vs 66% at 18 months (p=0.08).ConclusionsBoth anti-CTLA4 and anti-PD1 agents prompt a similar degree of in-field and out-of-field responses after iRT, although the global response rate and PFS were statistically higher in the anti-PD1 cohort. Further dedicated study and biological mechanistic assessment is required.Trial registration numbersNCT02239900andNCT02444741.

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Section: Introductionmentioning

confidence: 99%

Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials

Chen

Menon

Verma

et al. 2020

J Immunother Cancer

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“…Melanoma clinical research during the last 10 years has driven the most important changes in treatment approaches seen in oncology since ever. From being an orphan and neglected disease it has moved to the most pioneering tumor from which so many other cancer types are learning and developing new strategies 72 . Advanced disease has demonstrated an impressive treatment efficacy improvement passing from 5% to more then 50% survival benefit at 5 years.…”

Section: Resultsmentioning

confidence: 99%

Adjuvant Treatment of Melanoma: Recent Developments and Future Perspectives

et al. 2019

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For early melanoma, surgical excision is the treatment of choice and this strategy is initially curative for the majority of patients. However, only approximately 40-60% of patients who have surgery alone and higher risk stages, will be disease-free after 5 years of follow up, depending on the original III stage of the disease. These patients will relapse either with locoregional or disseminated disease. Adjuvant therapies are required to be able to reduce the recurrence rate on radically operated patients in these different initial stages of the disease. New treatments have appeared in the landscape of metastatic melanoma and this have opened to new potential scenarios in the adjuvant setting. In particular immunotherapy, immunocheckpoint inhibitors and target therapies have been recently published their potential advantage from the results obtained in the curative setting for stage IV, where the different mechanisms of action could even be potentially more active and more responsive due to the limited subclinical presence of disease in the patients after surgical complete resection.

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“…The average 5‐year survival rate for patients with metastatic CM is less than 10% . Several new targeted and immune therapies have shown antitumor activity with acceptable side effects in patients with advanced melanoma . Number and site of metastasis are among several factors that influence survival in patients with metastatic melanoma suggesting that close follow‐up imaging of patients with CM to detect low disease burden and at an early stage, coupled with new immune therapies may prolong survival for patients with high‐risk disease.…”

Section: Discussionmentioning

confidence: 99%