PMID- 35681675
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 11
DP  - 2022 May 30
TI  - Exploring Real World Outcomes with Nivolumab Plus Ipilimumab in Patients with 
      Metastatic Extra-Pulmonary Neuroendocrine Carcinoma (EP-NEC).
LID - 10.3390/cancers14112695 [doi]
LID - 2695
AB  - Background: Dual utilization of the immune checkpoint inhibitors (ICPIs) 
      nivolumab plus ipilimumab has demonstrated clinical promise in the treatment of 
      patients with refractory high-grade neuroendocrine neo-plasms (NENs) in phase II 
      clinical trials (DART SWOG 1609 and CA209), while single agent ICPIs have largely 
      been ineffective for these types of tumors. While both trials demonstrated 
      promising results in high grade NENs, there was no adequate description of the 
      association between tumor differentiation (high-grade well-differentiated 
      neuroendocrine tumor vs poorly-differentiated extra-pulmonary neuroendocrine 
      carcinoma (EP-NEC) and ICPI outcomes in the DART SWOG 1609 trial. Our study 
      reports on the effectiveness and toxicity profile of dual ICPIs in a real world 
      second-line EP-NEC patient population. Methods: Data on metastatic EP-NEC 
      patients, treated with either ICPIs (single and dual ICPIs) or chemo-therapy in 
      the second-line setting, were retrieved from databases of three comprehensive 
      cancer centers. Associations between treatment characteristics and outcomes, 
      including progression-free survival (PFS) and overall survival (OS), were 
      evaluated. Results: From 2007 to 2020, we identified 70 patients with metastatic 
      EP-NEC (predominantly of gastro-enteropancreatic origin), of whom 42 patients (23 
      males, 19 females, median age 62 years old) were eligible for the final analysis. 
      All patients were refractory to platinum etoposide doublet chemotherapy in the 
      first-line setting. The median PFS for patients who received dual ICPIs (11 
      patients), single agent ICPI (8 patients), and cytotoxic chemotherapy (23 
      patients) was 258 days, 56.5 days, and 47 days, respectively (p = 0.0001). Median 
      overall survival (OS) for those groups was not reached (NR), 18.7 months, and 
      10.5 months, respectively (p = 0.004). There were no significant differences in 
      treatment outcomes in patients according to tumor mismatch repair (MMR) or tumor 
      mutational burden (TMB) status. Grade 3-4 adverse events (AEs) were reported in 
      11.1% of the patients who received dual ICPIs; however, none of these AEs led to 
      permanent treatment discontinuation. Conclusions: In the second-line setting, 
      patients with EP-NECs treated with dual ICPIs (nivolumab plus ipilimumab) 
      experienced improved PFS and OS compared to patients treated with single agent 
      ICPI or cytotoxic chemotherapy. These results echo some of the current evidence 
      for ICPIs in grade 3 NENs and need to be validated in future prospective studies.
FAU - Mohamed, Amr
AU  - Mohamed A
AUID- ORCID: 0000-0002-6962-3535
AD  - Department of Medicine, Division of Hematology and Medical Oncology, University 
      Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 
      44106, USA.
FAU - Vijayvergia, Namrata
AU  - Vijayvergia N
AUID- ORCID: 0000-0001-6469-4759
AD  - Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA 
      19111, USA.
FAU - Kurian, Matthew
AU  - Kurian M
AUID- ORCID: 0000-0003-4015-5261
AD  - Department of Medicine, Division of Hematology and Medical Oncology, University 
      Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 
      44106, USA.
FAU - Liu, Lisa
AU  - Liu L
AUID- ORCID: 0000-0001-7521-9777
AD  - Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA 
      19111, USA.
FAU - Fu, Pingfu
AU  - Fu P
AUID- ORCID: 0000-0002-2334-5218
AD  - Department of Medicine, Division of Hematology and Medical Oncology, University 
      Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 
      44106, USA.
FAU - Das, Satya
AU  - Das S
AD  - Department of Medicine, Division of Hematology and Medical Oncology, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
LA  - eng
PT  - Journal Article
DEP - 20220530
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9179548
OTO - NOTNLM
OT  - checkpoint inhibitor therapy
OT  - chemotherapy
OT  - neuroendocrine carcinoma
OT  - nivolumab and ipilimumab
COIS- A.M. received an honorarium for consulting for Advanced Accelerator 
      Applications/Novartis, Ipsen and TerSera Therapeutics. S.D. received an 
      honorarium for consulting for Advanced Accelerator Applications/Novartis, Ipsen 
      and TerSera Therapeutics. N.V.: Consulting/Advisory role for Novartis, Tersera, 
      Ipsen, Astra Zeneca, ITM, Taiho, Halio Dx.
EDAT- 2022/06/11 06:00
MHDA- 2022/06/11 06:01
PMCR- 2022/05/30
CRDT- 2022/06/10 01:09
PHST- 2022/04/12 00:00 [received]
PHST- 2022/05/10 00:00 [revised]
PHST- 2022/05/24 00:00 [accepted]
PHST- 2022/06/10 01:09 [entrez]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/06/11 06:01 [medline]
PHST- 2022/05/30 00:00 [pmc-release]
AID - cancers14112695 [pii]
AID - cancers-14-02695 [pii]
AID - 10.3390/cancers14112695 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 May 30;14(11):2695. doi: 10.3390/cancers14112695.