Activity &amp; safety of spartalizumab (PDR001) in patients (pts) with advanced neuroendocrine tumors (NET) of pancreatic (Pan), gastrointestinal (GI), or thoracic (T) origin, &amp; gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who have progressed on prior treatment (Tx)

Yao, James C.; Strosberg, Jonathan R.; Fazio, Nicola; Pavel, Marianne; Ruszniewski, Philippe; Bergsland, Emily K.; Li, D.; Tafuto, Salvatore; Raj, Nitya; Campana, Davide; Hijioka, Susumu; Raderer, Markus; Guimbaud, Rosine; Gajate, Pablo; Pusceddu, Sara; Reising, Albert; Degtyarev, Evgeny; Mookerjee, Bijoyesh; Aimone, Paola; Singh, Simron

doi:10.1093/annonc/mdy293.001

Cited by 70 publications

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“…The phase II spartalizumab trial also includes a cohort of patients with well-differentiated gastrointestinal (N = 30) and pancreatic NET (N = 30) and a cohort of patients with poorly differentiated GEP-NEC (N = 20). In these cohorts, ORR was 0%, 3.0%, and 4.8%, respectively, showing a marginal activity in this setting [62].…”

Section: Immunotherapy In Gastroenteropancreatic Nensmentioning

confidence: 76%

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Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

Maggio

Manuzzi

Ricci

et al. 2020

Cancers

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Background: Neuroendocrine neoplasms are rare entities consisting of a heterogeneous group of tumors that can originate from neuroendocrine cells present in the whole body. Their different behavior, metastatic potential, and prognosis are highly variable, depending on site of origin, grade of differentiation, and proliferative index. The aim of our work is to summarize the current knowledge of immunotherapy in different neuroendocrine neoplasms and its implication in clinical practice. Results: Several studies evaluated the efficacy and safety of immunotherapy in neuroendocrine neoplasms, in any setting of treatment, alone or in combination. Studies led to approval in neuroendocrine neoplasia of the lung, in combination with chemotherapy as first-line treatment or as a single-agent in a third-line setting, and Merkel cell carcinoma as a single agent. Results in other settings have been disappointing so far. Conclusions: Immunotherapy seems a valid treatment option for high grade, poorly differentiated neoplasms. Future trials should explore the combination of immunotherapy with other agents, such as anti-angiogenic or other immunotherapy agents, in order to evaluate potential efficacy in low and intermediate grades, well differentiated tumors.

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Section: Immunotherapy In Gastroenteropancreatic Nensmentioning

confidence: 76%

“…The ORR was overall 7.4%, but it reached 20% in the thoracic NET cohort, suggesting some signal of activity in this setting. The most common Grade 3-4 adverse events were abdominal pain, anemia, dyspnea, and hypertension [62].…”

Section: Lcnec Typical and Atypical Carcinoidmentioning

confidence: 99%

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

Maggio

Manuzzi

Ricci

et al. 2020

Cancers

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“…High rate of mutations could result in the formation of neoantigens, which is hypothesized to enhance the anti-tumor immune response [ 37 ]. In NETs, both the anti-PD1 agents pembrolizumab and spartalizumab have proven to be safe, but the results are unsatisfactory in terms of activity [ 38 , 39 ]. We observed low somatic coding mutation per case for both NETs, but also higher mutation load (≥6 somatic mutations) for two TCs and four ACs.…”

Section: Discussionmentioning

confidence: 99%

Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups

Centonze

Biganzoli

Prinzi

et al. 2020

Cancers

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Lung neuroendocrine neoplasms (LNENs) represent a rare and heterogeneous population of lung tumors. LNENs incidence rate has increased dramatically over the past 30 years. The current World Health Organization LNENs classification (WHO 2015), distinguished four LNENs prognostic categories, according to their morphology, necrosis amount and mitotic count: typical carcinoid (TC), atypical-carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC). At present, due to their rarity and biological heterogeneity there is still no consensus on the best therapeutic approach. Next-generation-sequencing analysis showed that WHO 2015 LNENs classes, could be characterized also by specific molecular alterations: frequently mutated genes involving chromatin remodeling and generally characterized by low mutational burden (MB) are frequently detected in both TC and AC; otherwise, TP53 and RB1 tumor suppressor genes alterations and high MB are usually detected in LCNEC and SCLC. We provide an overview concerning gene mutations in each WHO 2015 LNENs class in order to report the current LNENs mutational status as potential tool to better understand their clinical outcome and to drive medical treatment.

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“…Another study of a PD-1 inhibitor, spartalizumab, consisted of 4 cohorts of roughly 30 patients each: GI NETs, pancreatic NETs, lung NETs (typical and atypical lung carcinoids), and poorly differentiated NECs of any primary site except lung (e.g., small cell lung cancer) and skin (Merkel cell) [10]. This study reported low response rates (< 10%) in all cohorts, except for a 20% response rate among lung NETs, particularly within the atypical carcinoid group.…”

Section: What Is the Role Of Checkpoint Inhibitors In Neuroendocrinementioning

confidence: 99%

Untitled

2020

Oncotarget

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Activity & safety of spartalizumab (PDR001) in patients (pts) with advanced neuroendocrine tumors (NET) of pancreatic (Pan), gastrointestinal (GI), or thoracic (T) origin, & gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who have progressed on prior treatment (Tx)

Cited by 70 publications

References 0 publications

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups

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