Phase II study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinomas: Results of Part B (pembrolizumab + chemotherapy).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4148-4148
Author(s):  
Jennifer A. Chan ◽  
Nitya Prabhakar Raj ◽  
Rahul Raj Aggarwal ◽  
Susan Calabrese ◽  
April DeMore ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Type I ◽  
First Line ◽  
Open Label ◽  
Total N ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

4148 Background: The efficacy of immune checkpoint inhibitor (CPI) therapy has not been established in extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). In small cell lung cancer, CPI therapy is approved for use in the first-line and salvage settings. We investigated the efficacy and safety of pembrolizumab (PEM)-based therapy in biomarker-unselected patients (pts) with EP-PDNECs. PEM alone (Part A, N=14) was inactive (ASCO GI 2019; Abstr#363). We now report the results of Part B (PEM plus chemotherapy). Methods: We conducted an open label, multicenter, phase 2 study of PEM-based therapy in pts with EP-PDNECs, excluding Merkel cell carcinoma and well differentiated grade 3 neuroendocrine tumors (NET), with disease progression on first-line systemic therapy. In Part B of this trial, patients were treated with PEM 200 mg IV every 3 week cycle plus dealers’ choice chemotherapy (chemo): weekly irinotecan (IRI, 125 mg/m2 day 1,8 of every 21 day cycle) or weekly paclitaxel (PAC, 80 mg/m2). After PEM/IRI safety lead-in (N=6), 16 additional pts (total N=22) were enrolled. This was based on a primary endpoint of objective response rate (ORR) by RECIST 1.1 and a plan to test Ha ORR 31% vs H0 ORR 10% with 80% power at a type I error rate of 0.05. Secondary endpoints include safety, overall survival (OS), and progression-free survival (PFS). Serial blood samples and baseline tumor biopsies were required in all pts. Results: Preliminary data from Part B are available. Of 22 pts enrolled, male/female 15/7; median age 57 years (range 34-75); ECOG PS 0/1: 10/12; 6 large cell, 8 small cell, 8 NOS. Primary sites of disease: GI 73%, GYN 5%, unknown 23%. Ki67 index (available for 18 pts) median 68% (range 30 to >95%). Chemo choice: 17 IRI (77%) and 5 PAC (23%). PEM/IRI was safe based on lead-in. Median number of cycles of therapy administered was 3 (range 0-13). Treatment-related Gr 3 or 4 AE occurred in 7 (32%) of 22 pts overall: 4 (18%) had at least one Gr 3 AE attributed to PEM (1 pt each with pain, ALT increase, or nausea; 2 with fatigue); 7 (32%) had at least one Gr 3/4 AE attributed to chemo (2 with fatigue, 2 with neutropenia; 1 each with pain, ALT increase, hyponatremia, diarrhea, nausea, and/or acute kidney injury). No grade 5 AE. ORR was 9%: PR in 2 pts (9%), SD 3 pts (14%), PD 13 pts (60%); 4 pts (18%) unevaluable (off study before first scheduled scan). Median PFS 2 mo. At last follow-up, 5 pts (23%) were alive with 1 pt still on treatment. Median OS 4 mo. Of 21 pts off treatment, 76% off for PD, 10% off for AE, 14% off for withdrawal of consent/other therapy. Conclusions: PEM + chemotherapy was not effective in this pretreated, biomarker-unselected population of EP-PDNECs arising in different organs. Biomarker studies are planned (Parts A/B). Clinical trial information: NCT03136055.

Phase II study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinomas: Results of Part A (pembrolizumab alone).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 363-363 ◽  
Author(s):  
Claire Mulvey ◽  
Nitya Prabhakar Raj ◽  
Jennifer A. Chan ◽  
Rahul Raj Aggarwal ◽  
Pelin Cinar ◽  
...  
Keyword(s):  
Early Death ◽  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Type I ◽  
Open Label ◽  
Poorly Differentiated ◽  
Grade 3 ◽  
Stage 1 ◽  
Neuroendocrine Carcinomas

363 Background: Immune checkpoint inhibitor (CPI) efficacy has not been established in extrapulmonary poorly-differentiated neuroendocrine carcinomas (EP-PDNECs). In small cell lung cancer, promising antitumor activity of CPI led to accelerated approval of nivolumab in 8/2018. We investigated the efficacy and safety of pembrolizumab (PEM)-based therapy in biomarker-unselected EP-PDNECs. Methods: Open label, multicenter, phase 2 study of PEM-based therapy in patients (pts) with EP-PDNECs, excluding Merkel cell carcinoma and well differentiated grade 3 NET, with progression on first-line systemic therapy, ECOG 0-1, and adequate hepatic and renal function. Enrollment via an adaptive Simon’s 2-stage design. Plan for 14 pts treated with PEM alone (Part A Stage 1) 200 mg IV every 3 weeks. If > 2 of 14 pts respond by week 18, then 21 additional pts enroll in Part A Stage 2, corresponding to H0 10% vs. H1 26% response rate (RR) at type I error 0.05 with power 80%. Otherwise study proceeds to Part B: PEM plus chemotherapy (dealer's choice of weekly irinotecan or paclitaxel). Primary endpoint is objective RR (ORR) by RECIST 1.1. Secondary endpoints include safety, overall survival, and progression-free survival (PFS). Serial blood samples and baseline tumor biopsies required in all pts for future biomarker studies. Results: Preliminary data from Part A Stage 1 are available. Of 14 pts enrolled, male/female 9/5; median age 63; 1 large cell, 11 small cell, 2 NOS. Primary site of disease: GI 43%, GU 29%, and other 29%. Median Ki67 80% (available for 9 pts). Best response: CR (1), PR (0), SD (2), PD (10), unevaluable (1; early death from sepsis) for ORR 7%. Median PFS was 58 days. Six (43%) pts went off study for early PD or clinical deterioration before first scheduled scan at 9 weeks. PEM was well tolerated with no grade 3-5 AEs attributed to therapy. At last follow up, 9 (64%) pts were alive with 1 pt still on treatment after 19 cycles. Conclusions: PEM monotherapy was not effective in this pretreated, biomarker-unselected population of EP-PDNECs arising in different organs. Part B (PEM plus chemotherapy) enrollment is ongoing. Biomarker studies are planned (Parts A/B). Clinical trial information: NCT03136055.

scholarly journals The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab

2021 ◽  
Vol 10 (5) ◽  
pp. 1005
Author(s):  
Edoardo Lenci ◽  
Luca Cantini ◽  
Federica Pecci ◽  
Valeria Cognigni ◽  
Veronica Agostinelli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Serum Albumin ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Albumin Concentration ◽  
Small Cell Lung ◽  
First Line

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 − GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.

Axitinib with or without dose titration for first-line metastatic renal cell carcinoma (mRCC): Unblinded results from a randomized phase II study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. LBA349-LBA349 ◽  
Author(s):  
Brian I. Rini ◽  
Viktor Gruenwald ◽  
Mayer N. Fishman ◽  
Bohuslav Melichar ◽  
Takeshi Ueda ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Type I Error ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Dose Titration ◽  
Type I ◽  
First Line ◽  
Antihypertensive Medications ◽  
Double Blind

LBA349 Background: Patients receiving the 5-mg twice daily (BID) axitinib starting dose exhibit variable drug exposure; prior pharmacokinetic analyses indicate higher exposure is associated with better outcomes in mRCC. Dose titration based on individual tolerability may optimize exposure and improve efficacy. Methods: Patients (N=213) with treatment-naïve mRCC received axitinib 5 mg BID for a 4-week lead-in period. Then, patients with 2 consecutive weeks of blood pressure ≤150/90 mmHg, no axitinib-related toxicities >grade 2, no dose reductions, and ≤2 antihypertensive medications were randomized (double-blind) to axitinib 5 mg BID + dose titration to 10 mg BID maximum with axitinib or placebo. Those not eligible for randomization continued axitinib 5 mg BID or lower. Primary endpoint was objective response rate (ORR) in randomized arms. Progression-free survival (PFS), overall survival, and safety were secondary endpoints. Assuming response rate under the null hypothesis is 0.15, this study had ≥80% power (1-sided type I error 10%) to detect a ≥25% absolute improvement in ORR with active vs placebo titration. Results: In all, 56 patients each were randomized to active and placebo titration arms, 91 were not randomized, and 10 withdrew during the lead-in period. As of Oct 12, 2012, ORR (95% confidence interval [CI]) was 54% (40–67) in the active titration arm vs 34% (22–48) in the placebo titration arm (1-sided P=0.019), and 59% (49–70) in the non-randomized arm. Median PFS (95% CI) from first dose was 14.5 mo (9.2–24.5) in the active titration arm vs 15.7 mo (8.3–19.4) in the placebo titration arm (hazard ratio favored active titration, 0.85; 95% CI, 0.54–1.35; 1-sided P=0.244), and 16.6 mo (11.2–22.5) in the non-randomized arm. Most frequent all-grade, all-causality adverse events in active titration, placebo titration, and non-randomized arms, respectively, were diarrhea (61% vs 63% vs 63%), hypertension (61% vs 43% vs 82%), and fatigue (45% vs 46% vs 54%). Conclusions: Axitinib is effective and well tolerated in first-line mRCC with prolonged median PFS in all treatment arms compared to historical controls. Axitinib dose titration significantly improved ORR vs placebo. Clinical trial information: NCT00835978.

A phase II study of a novel anti-tubulin, E7389, in patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7106-7106
Author(s):  
A. Das ◽  
A. Spira ◽  
N. Iannotti ◽  
M. Savin ◽  
E. Zang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Large Cell ◽  
Median Number ◽  
Synthetic Analog ◽  
Open Label ◽  
Best Response

7106 Background: E7389, a synthetic analog of halichondrin B that was isolated from a marine sponge, has broad anti-proliferative activity at nanomolar levels and a unique profile of tubulin interactions. Methods: This is an open-label, single-arm, stratified phase II study of E7389 in patients with measurable, recurrent and/or metastatic NSCLC who progressed during or after platinum-based doublet chemotherapy. E7389 (1.4 mg/m2) was administered as a bolus IV on days 1, 8, and 15 of a 28-day cycle to 72 patients (cohort 1) in stratum I (55 taxane pretreated patients) and stratum II (17 taxane-naive patients) and on Days 1 and 8 of a 21-day cycle (cohort 2), providing an additional 22 patients in stratum I. The primary efficacy endpoint was objective response rate to E7389 monotherapy. Results: As of 9 December 2005, 94 evaluable patients received E7389. Nineteen tumors were classified as squamous cell carcinomas, 39 as adenocarcinomas, and 36 were large cell carcinomas or unclassified. The median number of cycles completed was 3. Fifteen patients completed 6 or more cycles and 75 patients underwent tumor assessments after cycle 2. Major toxicities related to study drug included myelosuppression, nausea, fatigue, dehydration, arthralgias, dyspnea, and peripheral neuropathy. Based on RECIST criteria, 6 partial responses (PR) were observed among 94 evaluable patients (PR rate = 6.4%, 95% CI: 2.8%, 12.8%). For 33 patients the best response was stable disease (SD rate = 35.1%, 95% CI: 25.5%, 45.1%). Disease control rate (PR + SD) was 41.5% (95% CI: 31.4%, 51.7%). For cohort 1, the 12-week progression free survival rate was 57.2%. As of 9 December 2005, median PFS time was 108 days (95% CI = 55, min-max = 1–239+). Cohort 2 is being followed to estimate their 12-week PFS. The correlation of beta tubulin isotype, stathmin, microtubule-associated protein 4 (MAP4) and tau protein mRNA expression with tumor responses is on-going. Conclusions: Based on this data, E7389 has been shown to be safe and effective in the treatment of NSCLC patients. Updated information and results of molecular correlations of responses will be presented. [Table: see text]

Checkmate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (Nivo) plus ipilimumab (Ipi) versus oxaliplatin plus fluoropyrimidine in patients (Pts) with previously untreated advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS213-TPS213 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Antoine Adenis ◽  
Jean-Sebastien Aucoin ◽  
Carlo Barone ◽  
Narikazu Boku ◽  
...  
Keyword(s):  
Phase 1 ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Phase 3 ◽  
Multiple Tumor ◽  
Open Label Phase

TPS213 Background: The combination ofoxaliplatin and fluoropyrimidine is a standard-of-care (SOC) first-line treatment of pts with metastatic G/GEJ cancer, resulting in a median overall survival (OS) of 8–11 months and objective response rate (ORR) of 30%–50%. This is accompanied by up to 77% grade 3/4 toxicities. Therefore, new treatment options are needed to improve survival and decrease toxicity in G/GEJ cancer. Nivo, a fully human IgG4 monoclonal antibody (mAb) that targets programmed death 1 (PD-1) and ipi, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte–associated protein 4, have demonstrated manageable safety profiles and efficacy in multiple tumor types and may have a synergistic effect. In a phase 1/2 study in chemotherapy-refractory pts with G/GEJ/esophageal cancer with or without PD-1 ligand 1 (PD-L1) expression, second-line nivo 1 mg/kg + ipi 3 mg/kg demonstrated a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), median OS of 6.9 months, and a 34% OS rate at 12 months (Janjigian Y, et al. J Clin Oncol. 2016;34[suppl][abstract 4010]). This open-label, phase 3 trial will evaluate nivo + ipi as first-line therapy for pts with G/GEJ cancer (CheckMate 649; NCT02872116). Methods: In this study, 870 pts aged ≥ 18 years with untreated advanced or metastatic G/GEJ cancer with or without PD-L1 expression will be randomized to receive nivo + ipi (4 doses; followed by nivo monotherapy) or investigator’s choice of capecitabine/oxaliplatin (XELOX) or fluorouracil/leucovorin/oxaliplatin (FOLFOX). Tumor tissue for determination of PD-L1 status must be provided from ≤ 6 months before study treatment. Pts receiving chemotherapy or radiotherapy for G/GEJ cancer within the last 6 months or pts with suspected autoimmune disease, uncontrolled medical disorder, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ tumors. Secondary endpoints include OS in all pts and progression-free survival and time to symptom deterioration in all pts and pts with PD-L1+ tumors. Clinical trial information: NCT02872116.

Camrelizumab combined with capecitabine and oxaliplatin followed by camrelizumab and apatinib as first-line therapy for advanced or metastatic gastric or gastroesophageal junction cancer: Updated results from a multicenter, open label phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4031-4031 ◽  
Author(s):  
Lin Shen ◽  
Zhi Peng ◽  
Yan-Qiao Zhang ◽  
Jia Wei ◽  
Feng Wang ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy ◽  
Open Label Phase

4031 Background: Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for advanced or metastatic gastric cancer. Camrelizumab (SHR-1210, an anti–PD-1 antibody) shows promising anti-tumor activity in patients (pts) with advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer. Camrelizumab combined with CAPOX for untreated G/GEJ cancer was assessed as a part of an ongoing multicenter, open-label phase 2 trial (cohort 1), and encouraging preliminary results were reported. Here, we present the updated safety and efficacy data. Methods: In this cohort, systemic treatment naïve pts with HER2– advanced or metastatic G/GEJ adenocarcinoma were given camrelizumab 200 mg on Day 1, capecitabine 1000 mg/m2 bid on Days 1–14 and oxaliplatin 130 mg/m2 on Day 1 of each 21-day-cycle for 4 to 6 cycles followed by camrelizumab 200 mg every 3 weeks plus apatinib 375 mg qd until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Results: At data cutoff (Jan 20, 2019), 43 of the 48 enrolled pts were evaluable. Partial response was observed in 28 pts (65%), and 19 (44%) were confirmed. Stable disease in 14 pts and progressive disease in 10 pts were reported. Median estimates for duration of response and progression-free survival were not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 9 pts (21%), included neutropenia, diarrhea, rash and elevated ALT, whereas none of the TRAEs was fatal. Ten pts without progression after 4–6 cycles of camrelizumab and CAPOX combination therapy all received camrelizumab plus apatinib as sequential therapy, and no new safety signals were observed. Conclusions: The updated results confirmed that camrelizumab plus CAPOX followed by camrelizumab plus apatinib was well tolerated with noteworthy responses as first-line therapy in advanced or metastatic G/GEJ cancer pts. Expansion of this cohort in a phase 3 study are under way. Clinical trial information: NCT03472365.

Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4144-TPS4144 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Claudia Pauligk ◽  
Thorsten Oliver Goetze ◽  
Jorge Riera-Knorrenschild ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Type I Error ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Clinical Activity ◽  
Type I ◽  
First Line

TPS4144 Background: The majority of patients (pts) with gastroesophageal cancer present with inoperable or metastatic disease and there is a strong need for efficient and tolerable first-line (1L) treatment. Oxaliplatin-based regimens like FOLFOX have become one standard of care. However, median survival is still below 12 months. Results from trials using nivolumab plus ipilimumab treatment of subjects with advanced/metastatic GC and GEJ cancers demonstrated clinical activity, in pts whose tumors did or did not express PD-L1; in addition, nivolumab alone and in combination with ipilimumab demonstrated clinical benefits in various other tumor types. Based on this clinical experience, the AIO-STO-0417 trial (Moonlight) has been designed to evaluate the combination of chemotherapy with two checkpoint inhibitors in first-line therapy of pts with gastroesophageal adenocarcinoma. Methods: This is a prospective, multicenter, randomized, investigator-initiated phase II trial. Pts with Her2-negative, inoperable, advanced or metastatic gastric or esophagogastric junction cancer will be randomized 1:1 to 1L treatment with FOLFOX (Oxaliplatin 85 mg/m²; Leucovorin 400 mg/m²; 5FU 400 mg/m² on d1 of each treatment cycle and 5FU 1200 mg/m² continuous infusion over 24 hrs d1 and d2) every 2 weeks plus Nivolumab 240 mg every 2 weeks and Ipilimumab 1mg/kg every 6 weeks (Arm A) or FOLFOX alone (Arm B). Primary endpoint of the trial is progression-free survival based on the ITT population. Main secondary endpoints are overall survival, objective response rate, Safety and Quality of life (EORTC QLQ-C30). 118 pts (59 per arm) will be enrolled to provide 80% power for detecting an average HR of 0.68 using the log rank test at a one-sided type I error of 10%. At the date of submission, (Feb 2019), 28 of planned 118 pts are randomized. Clinical trial information: NCT03647969.

Pulmonary Neuroendocrine Carcinomas

2002 ◽  
Vol 126 (5) ◽  
pp. 545-553 ◽  
Author(s):  
Qin Huang ◽  
Alona Muzitansky ◽  
Eugene J. Mark
Keyword(s):  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
The Body ◽  
Low Grade ◽  
Typical Carcinoid ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Abstract Context.—Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. Objective.—To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. Patients.—To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. Results.—On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. Conclusion.—Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.

scholarly journals FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements

2020 ◽  
Vol 16 (30) ◽  
pp. 2385-2399 ◽  
Author(s):  
Tanios S Bekaii-Saab ◽  
Juan W Valle ◽  
Eric Van Cutsem ◽  
Lorenza Rimassa ◽  
Junji Furuse ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Survival Duration ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Duration Of Response

FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1–3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with FGFR2 rearrangements (NCT03656536). The primary end point is progression-free survival; secondary end points are objective response rate, overall survival, duration of response, disease control rate, safety and quality of life. Clinical Trial Registration: NCT03656536 ( ClinicalTrials.gov )

scholarly journals Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4152
Author(s):  
Melissa Frizziero ◽  
Alice Durand ◽  
Rodrigo G. Taboada ◽  
Elisa Zaninotto ◽  
Claudio Luchini ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Contributing Factors ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Extra Pulmonary ◽  
Neuroendocrine Carcinomas

Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in “real-world” treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; p = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; p = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, p = 0.015; and disease control rate; 59.7% vs. 79.6%, p = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, p = 0.016) and overall survival (OS) (adjusted-HR = 1.640, p = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (<55% vs. ≥55%) had significantly different PFS (adjusted-p = 0.021) and OS (adjusted-p = 0.051), with the non-SC subgroup with a Ki-67 index of <55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.

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