Advanced Neuroendocrine Carcinoma Research Articles

Combined use of albumin and neutrophil-to-lymphocyte ratio as new prognostic and predictive factor in patients with poorly differentiated neuroendocrine carcinomas.

e15543 Background: Outcomes of patients affected by advanced neuroendocrine carcinomas (NEC) with Ki-67 labeling index > 55% are heterogeneous regardless of the primary tumor site. We explored baseline inflammatory indexes and serum albumin levels to identify markers of response to standard first line chemotherapy. Methods: We retrospectively identified patients with advanced NEC treated with cisplatin (CP) or carboplatin (CB) and etoposide between 2015 and 2019 at the National Cancer Institute of Milan. Linear and Cox regressions were used to investigate, respectively, numeric and time-to-event outcomes. Maximization of log-rank statistics was used for optimal cutoffs finding. An artificial intelligence algorithm, random forest, was used to rank the impact of different clinical features on OS and PFS. Results: A total of 81 consecutive patients with different primary tumors (53 small cell lung carcinoma, 12 large cell neuroendocrine carcinoma, 10 gastrointestinal neuroendocrine carcinoma and 6 Merkel cell carcinoma) either treated with CP (n = 39) or CB (n = 42) were analyzed. Overall response rate (ORR), median progression free survival (PFS) and median overall survival (OS) were, respectively, 50.6%, 5.5 months (m) and 9.1m. Considered together, high serum albumin (SA > 3.5 g/dl) and low neutrophile-to-lymphocyte ratio (NLR < 3.59) identified a group of patients (n = 42) with longer median PFS and OS compared to the rest of the cohort (8.3m vs 1.5m, HR 3.58, CI 2.14-6.02, p < 0.001 for PFS and 12.6m vs 4.4m, HR 3.11, CI 1.88-5.18, p < 0.001 for OS); within this group a higher ORR (74% vs 36%, OR 5.01, CI 1.83-14.64, p = 0.002) was observed. Two multivariate models showed statistically significant associations of SA and NLR with PFS ( p = 0.017 and p = 0.005) and OS ( p = 0.016 and p = 0.036), independent of baseline ECOG performance status, age, sex, body mass index, smoking status, stage, hepatic tumor burden, primary site, histology, lactate dehydrogenase (LDH) serum levels, type of platinating agent and number of cycles. Two random forest models ranked SA, NLR and LDH as the most important factors for PFS and OS prediction. Conclusions: In the setting of advanced NEC with Ki-67 > 55% the combined use of SA and NLR identified two groups of patients with remarkably different outcomes, suggesting that these serum markers at baseline may have prognostic implications and be predictive of response to platinating agents. Prospective studies should validate these preliminary findings.

Neoadjuvant chemotherapy improves the survival of patients with neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma of the stomach.

The impact of neoadjuvant chemotherapy (NAC) on patients with neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) of the stomach is unclear. The aim of this retrospective study was to evaluate the effects of NAC on patients with these conditions. This study included patients with locally advanced NEC or MANEC of the stomach who underwent gastrectomy. Histologic and prognostic effects of NAC were assessed. The overall survival (OS) rate was used to compare treatment efficacies between NAC patients and surgery-first patients. Of the 69 patients included in this study, 20 received NAC and 49 underwent surgery first after diagnosis. A total of 13 patients responded to NAC (including 3 with complete remission and 10 with partial remission) and 7 patients acquired stable disease status according to the Response Evaluation Criteria in Solid Tumors version 1.1. One patient (5%) achieved a pathological complete response after NAC. Pathological tumor regression grades 1, 2, 3, 4, and 5 were observed in 1 (5%), 5 (25%), 3 (15%), 10 (50%), and 1 (5%) patient(s) with NAC, respectively. The incidence of postoperative complications was similar in the two groups. Patients in the NAC group demonstrated better OS than did patients in the surgery-first group (P = 0.032). Multivariate analyses showed that NAC, adjuvant chemotherapy, and the clinical N stage were independent factors affecting OS. In patients with locally advanced NEC and MANEC of the stomach, NAC significantly improved OS.

Treatment strategies for neuroendocrine carcinoma of the upper digestive tract.

Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy. Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12). Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3months for the 11 effective and 7 non-effective patients, respectively. A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.

Capecitabine, Oxaliplatin, Irinotecan, and Bevacizumab Combination Followed by Pazopanib Plus Capecitabine Maintenance for High-Grade Gastrointestinal Neuroendocrine Carcinomas

Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC. This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m, oxaliplatin 80 mg/m on day 1, CP 1000 mg/m twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate. Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed. First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.

Advanced neuroendocrine carcinoma (Merkel cell carcinoma) of the vulva: a case report and literature review

Neuroendocrine carcinomas (Merkel cell carcinomas) of the vulva are extremely rare tumours, with very few cases reported to date. Herein, a primary neuroendocrine carcinoma (Merkel cell carcinoma) ...

Neuroendocrine Carcinoma of the Cervix with Sister Mary Joseph's Nodule: About a Case and Literature Review

Neuroendocrine tumors are a rare and aggressive histological variant of the cervix, and they have several differences compared to other types of cervical cancer, in prognosis, diagnosis and treatment. In this paper we report the case of a 39-year-old patient that was taken care of in the medical oncology department at the Hassan II University Hospital Center, for an advanced neuroendocrine carcinoma of the cervix with a Sister Mary Joseph’s nodule. The aim of this work is to highlight this rare location of neuroendocrine tumors and their very aggressive character; by describing the different clinical, radiological and anatomopathological aspects of the primary tumor as well as umbilical metastasis.

Poorly differentiated neuroendocrine rectal carcinoma with uncommon immune-histochemical features and clinical presentation with a subcutaneous metastasis, treated with first line intensive triplet chemotherapy plus bevacizumab FIr-B/FOx regimen: an experience of multidisciplinary management in clinical practice

BackgroundNeuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1.Case presentationA 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months.Discussion and conclusionsThis case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.

Temozolomide monotherapy in patient of neuroendocrine carcinoma with resistant to platinum chemotherapy (Final Report)

Abstract Background Neuroendocrine carcinomas (NEC) (high grade Ki67 > 20%) were poor prognostic and lethal disease. Platinum-based chemotherapy is usually chosen as a first line treatment for advanced NEC. However, this efficacy is temporary and there is no standard second-line treatment. Temozolomide (TMZ) based chemotherapy is one of the effective treatment options for advanced NEC in foreign countries, however it was not approved for NEC by Japanese authorities. The aim of this study is the efficacy and safety of TMZ monotherapy for advanced NEC patients with resistant to platinum-based chemotherapy. Methods The dose of TMZ was 200mg/m2 from day1 to 5 every 4 weeks. This study was designed as prospective Phase II. Primary end point was response rate (RR) and secondary end point was disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. We also evaluated the prevalence of O6-methylguanine DNA methyltransferase (MGMT) in NEC and correlated MGMT deficiency with treatment response to TMZ by immunohistochemistry (IHC) as accompanying study. Results We recruited 13 cases pathologically diagnosed poorly differentiated and/or high grade NEC (man: 6, woman: 7, median age: 65). Primary lesions were pancreas (n = 3), stomach (3), duodenum (1), colon (1), gallbladder (1), liver (1), uterus (1), bladder (1), and primary unknown (1). Median of Ki-67 leveling index was 60% (range 22-90%). RR was 15.4% and DCR rate was 23.1% (PR: 2, SD: 1, PD: 10). PFS was 55 days (95% C.I. 29.7-80.3). OS was 214 days (95% C.I. 32.7-395.3) and OS from first line treatment was 547 days (429.2-664.8). There were no severe hematological adverse events, but Grade 3 nausea was occurred only one case (7.7%). One case (9.1%) was MGMT deficiency by IHC and this case achieved partial response. Conclusion TMZ monotherapy for advanced NEC was safety but marginally effective treatment for patient with resistant to platinum-based chemotherapy.

Safety and Efficacy of FOLFSIM Plus Toripalimab in the Treatment of Advanced or Metastatic Neuroendocrine Carcinoma

Safety and Efficacy of FOLFSIM Plus Toripalimab in the Treatment of Advanced or Metastatic Neuroendocrine Carcinoma

395P - A study of efficacy and safety with apatinib therapy in advanced neuroendocrine carcinoma patients

395P - A study of efficacy and safety with apatinib therapy in advanced neuroendocrine carcinoma patients

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience.

Background:Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit.Methods:The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test.Results:A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318–0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival.Conclusion:The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.

A real world study of efficacy and safety with apatinib therapy in advanced neuroendocrine carcinoma patients.

e14567Background: There is no standard therapeutic method for advanced neuroendocrine carcinoma patients after second line systemic therapy. It’s need novel effective therapies for these patients. ...

EP-1505: Multimodal management of locally advanced neuroendocrine cervical carcinoma

EP-1505: Multimodal management of locally advanced neuroendocrine cervical carcinoma

A case report of successful treatment of metastatic gastral neuroendocrine carcinoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib

Context: Neuroendocrine Tumor (NET) is arising from cells throughout the diffuse endocrine system. They comprise a broad family of tumors. Neuroendocrine Carcinoma (NEC) is a poorly differentiated and high-grade type. Advanced NEC has a poor prognosis due to a limited efficacy for chemotherapy and radiotherapy. Case Presentation: We present here a 51-year-old Chinese woman initially diagnosed with advanced gastral neuroendocrine carcinoma. She accepted everolimus as the first line treatment, but progression after 1 month. And then she received two different cytotoxic chemotherapy regimens. Unfortunately, the treatment failed. Then, she received apatinib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 that has been used in the treatment of patients with metastatic gastric cancer who progressed with 2 or more chemotherapy regimens. This patient was partially responsive to apatinib with a dose of 500 mg daily. Tolerated drug-related side effects were observed. Conclusion: Our findings indicate that some cases of neuroendocrine carcinoma may be responsive to antiangiogenic agent apatinib. Further large-scale prospective studies are needed to optimize the treatment.

Systemic chemotherapy with pronounced efficacy and neutropenia in a granulocyte-colony stimulating factor-producing advanced gastric neuroendocrine carcinoma.

An advanced granulocyte-colony stimulating factor (G-CSF)-producing tumor is rare, and it exhibits leukocytosis in association with high serum G-CSF levels. A 67-year-old male with a 1-month history of bloody emesis and black stools was revealed to exhibit leukocytosis, anemia and a high serum concentration of G-CSF. During a gastrointestinal endoscopy, an ulcerating tumor was identified in the stomach. Computed tomography and a fluorodeoxyglucose-positron emission tomography scan demonstrated direct invasion of the gastric tumor into the transverse colon, regional lymphadenopathy, lung nodules and diffuse high uptake of FDG in bone marrow. The histological diagnosis was a G-CSF-producing neuroendocrine carcinoma (NEC) (tumor 4b, node 2, metastasis 1, pulmonary, clinical stage IV). Systemic chemotherapy consisting of cisplatin and irinotecan was started. Common terminology criteria of adverse events grade 3 tumor lysis syndrome and gastric penetration appeared. Grade 4 neutropenia lasted for 10 days despite intensive G-CSF administration. Prominent shrinkage of the primary and the metastatic tumors was observed subsequent to 3 cycles of chemotherapy. Total gastrectomy and resection of the transverse colon were subsequently performed. Systemic chemotherapy was effective for a G-CSF-producing advanced gastric NEC with careful monitoring and appropriate supportive care for severe adverse events.

Successful Management of Recurrent Neuroendocrine Carcinoma of the Sphenoid Sinus Using Octreotide LAR: A Case Report

Overexpression of somatostatin (SST) receptors detected in most neuroendocrine carcinomas (NECs) appears to play an important role in the pathogenesis of NECs. Inhibition of SST receptors with SST analogues has been proved to be effective in various types of neuroendocrine tumors. We present here a case report of a 59-year-old female with recurrent sphenoidal NEC treated with SST analogues Octreotide and Octreotide long-acting release (LAR) as a salvage therapy. Improvement of optic nerve compression and quality of life (QOL) were observed along with a 77 months of progression free survival. This result suggests that OCT/OCT LAR may be a new approach to treating advanced NECs of the paranasal sinuses.

ISY-12-5 - Current status and perspective of systemic chemotherapies for GEP-NEC

According to the World Health Organization grading system for neuroendocrine neoplasms, neuroendocrine carcinoma (NEC) is a poorly differentiated, high-grade malignant tumor, including small and large cell carcinoma. The primary sites of NEC vary, with gastroenteropancreatic NEC (GEP-NEC) accounting for 20%–68% of extra-pulmonary NEC. Treatment guidelines for advanced extra-pulmonary NEC recommend platinum-based chemotherapy regimens, which are suitable for small cell lung carcinoma. There are two large-scale, multicenter retrospective analyses of advanced GEP-NEC: the NORDIC NEC study [Sorbye H et al. Ann Oncol. 2013;24(1)] and the Japanese study [Yamaguchi et al. Cancer Sci. 2014;105(9)]. In both studies, GEP-NEC prognoses varied according to primary organs. Although only etoposide plus cisplatin regimen (EP) was the mainstream first line chemotherapy in NORDIC, EP and irinotecan plus cisplatin regimen (IP) were commonly used in Japan. Both regimens (EP, IP) have been demonstrated to show favorable efficacy and have been acknowledged as de facto standard regimens for advanced NEC, although it remains unclear which of the two regimens might yield more favorable outcomes. Therefore, a phase III study comparing EP and IP in terms of overall survival for patients with recurrent or unresectable GEP-NEC (TOPIC-NEC, UMIN000014795) has been commenced by the Japan Clinical Oncology Group (JCOG). The sample size was set as 140 (70 patients per arm). For second line regimens, amrubicin, irinotecan, and S-1 were commonly utilized in Japan, but no standard regimens have been established. A multicenter phase II study to evaluate the efficacy of everolimus in pancreatic NEC patients who are unresponsive to/intolerant of platinum-based regimens (NECTOR: UMIN000012752) is currently in progress.

Abstract 3116: MGMT immunohistochemistry (IHC) as a biomarker for response to combination therapy with capecitabine and temozolomide (C/T) in patients (pts) with advanced neuroendocrine carcinomas (aNEC)

Abstract Introduction: Tumor O6-methylguanine-methyltransferase (MGMT) reverses temozolomide-induced DNA injury, and low MGMT tumor expression has been shown as a predictor of response to temozolomide in glioblastoma. C/T therapy induces partial responses in up to 70% of pts with grade 1-2 pancreatic NEC but the role of MGMT expression as a predictor is unclear. We evaluated MGMT expression by IHC as a prognostic and predictive biomarker for pts with aNEC of all grades and primary sites treated with C/T. Methods: A retrospective review was carried out at Ohio State University of 29 pts with aNEC who received C/T therapy from 2009 to 2013 and who were evaluable for RECIST response. MGMT expression was assessed when available by IHC on pre-treatment tumor samples to test the hypothesis that low MGMT expression (<10%) predicts response to C/T therapy vs high levels (≥10%). Results: Of 29 pts, primary NEC site was pancreas in 18 pts, and non-pancreas in 11 pts. Objective response, progression-free survival (PFS) and overall survival (OS) data are outlined in the Table. Partial response (PR) rate was 50% in pts with pancreas primary vs 18% for non-pancreas primary. High PRs were observed in pts with grade 3 NEC (57%). Median PFS in the MGMT-low group was 16.6 months vs 9.5 months in the MGMT-high group (p = 0.19). Median OS in the MGMT low group was 42.9 months vs 18.1 months in the MGMT-high group (p = 0.16). There was a trend toward higher rate of PR (63%) in pts whose tumors had low levels of MGMT expression compared to those with high levels (17%) (p = 0.18). Conclusion: We observed a trend towards increased PR, median PFS, and median OS in aNEC pts whose tumors had low MGMT protein expression by IHC. The small sample size likely limited the statistical significance of the data. Results of this trial serve as strong rationale for future prospective trials to clarify role of MGMT expression in choosing C/T therapy for pts with NEC. Objective response rate, progression free survival (PFS) and overall survival (OS)N%PR%SD%PDMedian PFSp-valueMedian OSp-valueAll patients2938521013.029.3Low MGMT by IHC (<10%)126238016.60.1942.90.16High MGMT by IHC (≥10%)81767179.518.1Well-differentiated tumor grade (Ki-67 <3%)74357020.00.34NR0.027Moderately differentiated tumor grade (Ki-67 3-20%)13316189.525.9Poorly-differentiated tumor grade (Ki-67 >20%)75714298.413.1 Citation Format: Dwight Owen, Andrew J. Alexander, Lai Wei, Jessica Hemminger, Manisha H. Shah. MGMT immunohistochemistry (IHC) as a biomarker for response to combination therapy with capecitabine and temozolomide (C/T) in patients (pts) with advanced neuroendocrine carcinomas (aNEC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3116.

オクトレオチドによる術後補助療法の有効性が示唆される直腸NECの1例

オクトレオチドによる術後補助療法の有効性が示唆される直腸NECの1例

R20 - Carboplatin and etoposide chemotherapy in extrapulmonary poorly differentiated neuroendocrine carcinomas

Background: Extrapulmonary poorly differentiated neuroendocrine carcinomas (NECs) clinically resemble a small cell lung cancer (SCLC), where carboplatin has been reported as active as cisplatin, combined with etoposide. We studied carboplatin/etoposide combination in patients with extrapulmonary NEC. Patients and methods: Consecutive patients with histological diagnosis of extrapulmonary unresectable locally advanced or metastatic NEC were enrolled. Overall response rate (ORR) was primary endpoint, whereas disease control rate (DCR), toxicity, progression free survival (PFS) and overall survival (OS) were secondary endpoints. Results: Forty-six patients were treated with Etoposide 100 mg/m2/day over three days and Carboplatin AUC 4-6 on day 1, every three weeks. Median age was 58 years (range 23-75). Thirty-nine patients were untreated and 7 pre-treated. Overall response rate was 54% (6% complete responses and 48% partial responses). Disease control rate was 78% (ORR + stable disease). Neutropenia was the most frequent grade 3-4 toxicity (22%), with 4 episodes of febrile neutropenia (9%). All type grade 3-4 toxicities occurred in the 33% of patients, leading to chemotherapy discontinuation in 2 cases (4%). Globally, PFS was 5 months (95% CI: 4.2 - 6.9) and OS 14 months (95% CI: 11.5 - 21.1). Conclusions: Carboplatin/etoposide combination is active and manageable in patients with extrapulmonary NEC. In a cross-study comparison, it is worth noting that our activity data are similar to, or even higher than, those reported for cisplatin/etoposide. Based on different toxicity profile, carboplatin could be considered as a possible alternative to cisplatin in this clinical setting.