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Clinical Studies

Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas

British Journal of Cancer (2023)Cite this article

Subjects

Abstract

Background

To date, single-agent immune checkpoint inhibitor (CPI) therapy has proven to be ineffective against biomarker-unselected extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). The efficacy of CPI in combination with chemotherapy remains under investigation.

Methods

Patients with advanced, progressive EP-PDNECs were enrolled in a two-part study of pembrolizumab-based therapy. In Part A, patients received pembrolizumab alone. In Part B, patients received pembrolizumab plus chemotherapy. Primary endpoint: objective response rate (ORR). Secondary endpoints: safety, progression-free survival (PFS) and overall survival (OS). Tumours were profiled for programmed death-ligand 1 expression, microsatellite-high/mismatch repair deficient status, mutational burden (TMB), genomic correlates. Tumour growth rate was evaluated.

Results

Part A (N = 14): ORR (pembrolizumab alone) 7% (95% CI, 0.2–33.9%), median PFS 1.8 months (95% CI, 1.7–21.4), median OS 7.8 months (95% CI, 3.1–not reached); 14% of patients (N = 2) had grade 3/4 treatment-related adverse events (TRAEs). Part B (N = 22): ORR (pembrolizumab plus chemotherapy) 5% (95% CI, 0–22.8%), median PFS 2.0 months (95% CI, 1.9–3.4), median OS 4.8 months (95% CI, 4.1–8.2); 45% of patients (N = 10) had grade 3/4 TRAEs. The two patients with objective response had high-TMB tumours.

Discussion

Treatment with pembrolizumab alone and pembrolizumab plus chemotherapy was ineffective in advanced, progressive EP-PDNECs.

Clinical trial registration

ClinicalTrials.gov NCT03136055.

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Fig. 1: Study schema.
Fig. 2: Tumour responses and clinical outcomes.
Fig. 3: Pre- and on-treatment tumour growth rate.

Data availability

The data generated and analysed for this study are available within this manuscript, and the accompanying tables and figures, with the exception of identifiable information. Any additional inquiries should be referred to the corresponding author.

References

  1. Dasari A, Mehta K, Byers LA, Sorbye H, Yao JC. Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: a SEER database analysis of 162,983 cases. Cancer. 2018;124:807–15.

    Article  PubMed  Google Scholar 

  2. Shia J, Tang LH, Weiser MR, Brenner B, Adsay NV, Stelow EB, et al. Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity? Am J Surg Pathol. 2008;32:719–31.

    Article  PubMed  Google Scholar 

  3. Volante M, Birocco N, Gatti G, Duregon E, Lorizzo K, Fazio N, et al. Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues. Hum Pathol. 2014;45:665–73.

    Article  PubMed  Google Scholar 

  4. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39:707–12.

    Article  PubMed  Google Scholar 

  5. Smith J, Reidy-Lagunes D. The management of extrapulmonary poorly differentiated (high-grade) neuroendocrine carcinomas. Semin Oncol. 2013;40:100–8.

    Article  PubMed  Google Scholar 

  6. Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, et al. Poorly differentiated neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 44 cases. Am J Surg Pathol. 2014;38:437–47.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Strosberg JR, Coppola D, Klimstra DS, Phan AT, Kulke MH, Wiseman GA, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010;39:799–800.

    Article  PubMed  PubMed Central  Google Scholar 

  8. McGarrah PW, Leventakos K, Hobday TJ, Molina JR, Finnes HD, Westin GF, et al. Efficacy of second-line chemotherapy in extrapulmonary neuroendocrine carcinoma. Pancreas. 2020;49:529–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–9.

    Article  CAS  PubMed  Google Scholar 

  10. Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394:1929–39.

    Article  CAS  PubMed  Google Scholar 

  11. Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csoszi T, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol. 2020;38:2369–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016;17:883–95.

    Article  CAS  PubMed  Google Scholar 

  13. Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, et al. Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort. J Thorac Oncol. 2020;15:426–35.

    Article  CAS  PubMed  Google Scholar 

  14. Chung HC, Piha-Paul SA, Lopez-Martin J, Schellens JHM, Kao S, Miller WH, et al. Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol. 2020;15:618–27.

    Article  CAS  PubMed  Google Scholar 

  15. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, et al. Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017;35:3823. -+

    Article  CAS  PubMed  Google Scholar 

  16. Vijayvergia N, Dasari A, Deng MY, Litwin S, Al-Toubah T, Alpaugh RK, et al. Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. Br J Cancer. 2020;122:1309–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yao JC, Strosberg J, Fazio N, Pavel ME, Bergsland E, Ruszniewski P, et al. Spartalizumab in metastatic, well/poorly-differentiated neuroendocrine neoplasms. Endocr Relat Cancer. 2021;28:161–72.

  18. Patel SP, Othus M, Chae YK, Giles FJ, Hansel DE, Singh PP, et al. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART SWOG 1609) in patients with nonpancreatic neuroendocrine tumors. Clin Cancer Res. 2020;26:2290–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Capdevila J, Landolfi S, Hernando J, Teule A, Garcia-Carbonero R, Custodio A, et al. Durvalumab plus tremelimumab in patients with grade 3 neuroendocrine neoplasms of gastroenteropancreatic origin: updated results from the multicenter phase II DUNE trial (GETNE 1601). Ann Oncol. 2021;32:S914–S5.

    Article  Google Scholar 

  20. Klein O, Kee D, Markman B, Michael M, Underhill C, Carlino MS, et al. Immunotherapy of ipilimumab and nivolumab in patients with advanced neuroendocrine tumors: a subgroup analysis of the CA209-538 clinical trial for rare cancers. Clin Cancer Res. 2020;26:4454–9.

    Article  CAS  PubMed  Google Scholar 

  21. Girard N, Mazieres J, Otto J, Lena H, Lepage C, Egenod T, et al. Nivolumab (nivo) +/- ipilimumab (ipi) in pre-treated patients with advanced, refractory pulmonary or gastroenteropancreatic poorly differentiated neuroendocrine tumors (NECs) (GCO-001 NIPINEC). Ann Oncol. 2021;32:S1318. -S

    Article  Google Scholar 

  22. Patel SP, Mayerson E, Chae YK, Strosberg J, Wang J, Konda B, et al. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: high-grade neuroendocrine neoplasm cohort. Cancer Am Cancer Soc. 2021;127:3194–201.

    CAS  Google Scholar 

  23. Owen DH, Benner B, Wei L, Sukrithan V, Goyal A, Zhou Y, et al. Efficacy of nivolumab and temozolomide in advanced neuroendocrine neoplasms (NENs) in a phase 2 clinical trial. J Clin Oncol. 2022;40:4121.

  24. Riesco-Martinez MC, Capdevila J, Alonso V, Jimenez-Fonseca P, Teule A, Grande E, et al. Nivolumab plus platinum-doublet chemotherapy as first-line therapy in unresectable, locally advanced or metastatic G3 neuroendocrine Neoplasms (NENs) of the gastroenteropancreatic (GEP) tract or unknown (UK) origin: Preliminary results from the phase II NICE-NEC trial (GETNE T1913). Ann Oncol. 2021;32:S908–S9.

    Article  Google Scholar 

  25. Capdevila J, Teule A, Lopez C, Garcia-Carbonero R, Benavent M, Custodio A, et al. A multi-cohort phase II study of durvalumab plus tremelimumab for the treatment of patients (pts) with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic or lung origin: the DUNE trial (GETNE 1601). Ann Oncol. 2020;31:S770–S1.

    Article  Google Scholar 

  26. Fottner C, Apostolidis L, Ferrata M, Krug S, Michl P, Schad A, et al. A phase II, open label, multicenter trial of avelumab in patients with advanced, metastatic high-grade neuroendocrine carcinomas NEC G3 (WHO 2010) progressive after first-line chemotherapy (AVENEC). J Clin Oncol. 2019;37:4103.

  27. Zhang P, Lu M, Li J, Shen L. Efficacy and safety of PD-1 blockade with JS001 in patients with advanced neuroendocrine neoplasms: a non-randomized, open-label, phase Ib trial. Ann Oncol. 2018;29:468.

    Article  Google Scholar 

  28. Patel SP, Mayerson E, Chae YK, Strosberg J, Wang J, Konda B, et al. SWOG S1609-A phase 2 basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors: a high-grade neuroendocrine neoplasm cohort. Cancer. 2021;127:3194–201.

    Article  CAS  PubMed  Google Scholar 

  29. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  30. Cheng DT, Mitchell TN, Zehir A, Shah RH, Benayed R, Syed A, et al. Memorial sloan kettering-integrated mutation profiling of actionable cancer targets (MSK-IMPACT) a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gnirke A, Melnikov A, Maguire J, Rogov P, LeProust EM, Brockman W, et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat Biotechnol. 2009;27:182–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29:3085–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wagle N, Berger MF, Davis MJ, Blumenstiel B, DeFelice M, Pochanard P, et al. High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov. 2012;2:82–93.

    Article  CAS  PubMed  Google Scholar 

  34. Niu B, Ye K, Zhang Q, Lu C, Xie M, McLellan MD, et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics. 2014;30:1015–6.

    Article  CAS  PubMed  Google Scholar 

  35. Afshar AR, Damato BE, Stewart JM, Zablotska LB, Roy R, Olshen AB, et al. Next-generation sequencing of uveal melanoma for detection of genetic alterations predicting metastasis. Transl Vis Sci Technol. 2019;8:18.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Natesan D, Zhang L, Martell HJ, Jindal T, Devine P, Stohr B, et al. APOBEC mutational signature and tumor mutational burden as predictors of clinical outcomes and treatment response in patients with advanced urothelial cancer. Front Oncol. 2022;12:816706.

    Article  PubMed  PubMed Central  Google Scholar 

  37. MacConaill LE, Garcia E, Shivdasani P, Ducar M, Adusumilli R, Breneiser M, et al. Prospective enterprise-level molecular genotyping of a cohort of cancer patients. J Mol Diagn. 2014;16:660–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Garcia EP, Minkovsky A, Jia Y, Ducar MD, Shivdasani P, Gong X, et al. Validation of OncoPanel: a targeted next-generation sequencing assay for the detection of somatic variants in cancer. Arch Pathol Lab Med. 2017;141:751–8.

    Article  CAS  PubMed  Google Scholar 

  39. Ferte C, Fernandez M, Hollebecque A, Koscielny S, Levy A, Massard C, et al. Tumor growth rate is an early indicator of antitumor drug activity in phase I clinical trials. Clin Cancer Res. 2014;20:246–52.

    Article  CAS  PubMed  Google Scholar 

  40. Ferte C, Koscielny S, Albiges L, Rocher L, Soria JC, Iacovelli R, et al. Tumor growth rate provides useful information to evaluate sorafenib and everolimus treatment in metastatic renal cell carcinoma patients: an integrated analysis of the TARGET and RECORD phase 3 trial data. Eur Urol. 2014;65:713–20.

    Article  CAS  PubMed  Google Scholar 

  41. Dromain C, Pavel ME, Ruszniewski P, Langley A, Massien C, Baudin E, et al. Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors. BMC Cancer. 2019;19:66.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lamarca A, Crona J, Ronot M, Opalinska M, Lopez Lopez C, Pezzutti D, et al. Value of tumor growth rate (TGR) as an early biomarker predictor of patients’ outcome in neuroendocrine tumors (NET)—the GREPONET study. Oncologist. 2019;24:e1082–e90.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lamarca A, Ronot M, Moalla S, Crona J, Opalinska M, Lopez CL, et al. Tumor growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumors: the GREPONET-2 study. Clin Cancer Res. 2019;25:6692–9.

    Article  PubMed  Google Scholar 

  44. Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res. 2019;25:3753–8.

    Article  CAS  PubMed  Google Scholar 

  45. Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21:1353–65.

    Article  CAS  PubMed  Google Scholar 

  46. Andre T, Berton D, Curigliano G, Jimenez-Rodriguez B, Ellard S, Gravina A, et al. Efficacy and safety of dostarlimab in patients (pts) with mismatch repair deficient (dMMR) solid tumors: analysis of 2 cohorts in the GARNET study. J Clin Oncol. 2022;40:2587.

    Article  Google Scholar 

  47. Su X, Zhou X, Xiao C, Peng W, Wang Q, Zheng Y. Complete response to immunotherapy combined with chemotherapy in a patient with gynecological mixed cancer mainly composed of small cell neuroendocrine carcinoma with high tumor mutational burden: a case report. Front Oncol. 2022;12:750970.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kang NW, Tan KT, Li CF, Kuo YH. Complete and durable response to nivolumab in recurrent poorly differentiated pancreatic neuroendocrine carcinoma with high tumor mutational burden. Curr Oncol. 2021;28:4587–96.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Stimes N, Stanbery L, Albrethsen M, Trivedi C, Hamouda D, Dworkin L, et al. Small-cell breast carcinoma with response to atezolizumab: a case report. Immunotherapy. 2022;14:669–74.

  50. Ricco B, Salati M, Reggiani Bonetti L, Dominici M, Luppi G. PD-1 blockade in deficient mismatch repair mixed adenoneuroendocrine carcinoma of the stomach: new hope for an orphan disease. Tumori. 2020;106:NP57–NP62.

    Article  PubMed  Google Scholar 

  51. Stueger A, Winder T, Tinguely M, Petrausch U, Helbling D. Metastatic mixed adenoneuroendocrine carcinoma of the colon with response to immunotherapy with pembrolizumab: a case report. J Immunother. 2019;42:274–7.

    Article  CAS  PubMed  Google Scholar 

  52. Whitman J, Kardosh A, Diaz L Jr, Fong L, Hope T, Onodera C, et al. Complete response and immune-mediated adverse effects with checkpoint blockade: treatment of mismatch repair-deficient colorectal neuroendocrine carcinoma. JCO Precis Oncol. 2019;3:1–7.

    PubMed  Google Scholar 

  53. Puccini A, Poorman K, Salem ME, Soldato D, Seeber A, Goldberg RM, et al. Comprehensive genomic profiling of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Clin Cancer Res. 2020;26:5943–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Venizelos A, Elvebakken H, Perren A, Nikolaienko O, Deng W, Lothe IMB, et al. The molecular characteristics of high-grade gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer. 2021;29:1–14.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Raj N, Shah R, Stadler Z, Mukherjee S, Chou J, Untch B, et al. Real-time genomic characterization of metastatic pancreatic neuroendocrine tumors has prognostic implications and identifies potential germline actionability. JCO Precis Oncol. 2018;2:1–18.

  56. Sun F, Grenert JP, Tan L, Van Ziffle J, Joseph NM, Mulvey CK, et al. Checkpoint inhibitor immunotherapy to treat temozolomide-associated hypermutation in advanced atypical carcinoid tumor of the lung. JCO Precis Oncol. 2022;6:e2200009.

    Article  PubMed  Google Scholar 

  57. Lee SM, Sung CO. Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas. Sci Rep. 2021;11:6203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yachida S, Totoki Y, Noe M, Nakatani Y, Horie M, Kawasaki K, et al. Comprehensive genomic profiling of neuroendocrine carcinomas of the gastrointestinal system. Cancer Discov. 2022;12:692–711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dromain C, Loaiza-Bonilla A, Mirakhur B, Beveridge TJR, Fojo AT. Novel tumor growth rate analysis in the randomized CLARINET study establishes the efficacy of lanreotide depot/autogel 120 mg with prolonged administration in indolent neuroendocrine tumors. Oncologist. 2021;26:e632–e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Weisbrod AB, Kitano M, Thomas F, Williams D, Gulati N, Gesuwan K, et al. Assessment of tumor growth in pancreatic neuroendocrine tumors in von Hippel Lindau syndrome. J Am Coll Surg. 2014;218:163–9.

    Article  PubMed  Google Scholar 

  61. Dromain C, Sundin A, Najran P, Vidal Trueba H, Dioguardi Burgio M, Crona J, et al. Tumor growth rate to predict the outcome of patients with neuroendocrine tumors: performance and sources of variability. Neuroendocrinology. 2021;111:831–9.

    Article  CAS  PubMed  Google Scholar 

  62. Pettersson OJ, Fross-Baron K, Crona J, Sundin A. Tumor growth rate in pancreatic neuroendocrine tumor patients undergoing PRRT with 177Lu-DOTATATE. Endocr Connect. 2021;10:422–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ji Z, Peng Z, Gong J, Zhang X, Li J, Lu M, et al. Hyperprogression after immunotherapy in patients with malignant tumors of digestive system. BMC Cancer. 2019;19:705.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Ramon-Patino JL, Schmid S, Lau S, Seymour L, Gaudreau PO, Li JJN, et al. iRECIST and atypical patterns of response to immuno-oncology drugs. J Immunother Cancer. 2022;10:e004849.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Al-Toubah T, Halfdanarson T, Gile J, Morse B, Sommerer K, Strosberg J. Efficacy of ipilimumab and nivolumab in patients with high-grade neuroendocrine neoplasms. ESMO Open. 2022;7:100364.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We wish to thank all of the patients participating in this study and their caregivers, along with the investigators and research study teams at UCSF, MSK and DFCI. In addition, we would like to thank Merck for supporting this multicenter study through the Merck Investigator Studies Programme.

Funding

This work was supported and funded by Merck & Co.; additional support provided by the National Cancer Institute of the National Institutes of Health under Award Numbers P30CA082103 (USCF), P30CA008748 (MSK), and P30CA006516 (DFCI).

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  1. These authors contributed equally: Nitya Raj, Jennifer A. Chan.

Authors and Affiliations

  1. Memorial Sloan Kettering (MSK) Cancer Center, New York, NY, USA

    Nitya Raj, April DeMore, Sippy Punn & Diane Reidy-Lagunes

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Jennifer A. Chan, Kimberly Perez & Sofia Von Fedak

  3. University of California San Francisco (UCSF), San Francisco, CA, USA

    Stephanie J. Wang, Rahul R. Aggarwal, Susan Calabrese, Lawrence Fong, Jennifer Grabowsky, Thomas A. Hope, Kanti Pallav Kolli, Claire K. Mulvey, Pamela N. Munster, Li Zhang & Emily K. Bergsland

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Contributions

NR, JAC and EKB conceived/designed the work that led to this submission, acquired data, and interpreted the results. SJW acquired data and interpreted results. RRA, SC, LF, JG, TAH, KPK, CKM, PNM, KP, DR-L and LZ interpreted the results. AM, SP and SvF acquired the data. All authors of this manuscript participated in drafting and/or revising the manuscript and approved the final manuscript version. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding authors

Correspondence to Nitya Raj or Emily K. Bergsland.

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Competing interests

Dr. Nitya Raj: research funding (ITM, Corcept Therapeutics), consulting/advisory boards (Ipsen Pharma, HRA Pharma, Progenics Pharmaceuticals, AAA). Dr. Jennifer Chan: consulting/advisory boards (TerSera, AAA, Curium), honorarium (Ipsen), stock ownership (Merck). Dr. Rahul Aggarwal: research funding (Merck). Dr. Lawrence Fong: research funding (Roche/Genentech, Abbvie, Bavarian Nordic, Bristol Myers Squibb, Dendreon, Janssen, Merck, Partner Therapeutics), advisory boards (Actym, Allector, Astra Zeneca, Atreca, Bioalta, Bolt, Bristol Myer Squibb, Daiichi Sankyo, Immunogenesis, Innovent, Merck, Merck KGA, Nutcracker, RAPT, Scribe, Senti, Soteria, Sutro, Roche/Genentech). Dr. Thomas Hope: research funding (Clovis Oncology, GE Healthcare, Philips, AAA), consulting (Bayer, Curium, ITM, RayzeBio), advisory boards (Blue Earth Diagnostics, Ipsen), stock ownership (RayzeBio). Dr. Claire Mulvey: research funding (Genentech). Dr. Pamela Munster: research funding (Merck). Dr. Kimberly Perez: consulting/scientific advisory boards (Lantheus, Helsinn/QED). Dr. Diane Reidy-Lagunes: research funding (Merck, Ipsen, Novartis). The remaining authors declare no competing interests.

Ethics approval and consent to participate

The study was reviewed by the University of California San Francisco (UCSF), Memorial Sloan Kettering Cancer Center (MSK), and Dana-Farber Cancer Institute (DFCI) Institutional Review Boards and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. All patients provided written informed consent before study enrolment.

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Raj, N., Chan, J.A., Wang, S.J. et al. Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas. Br J Cancer (2023). https://doi.org/10.1038/s41416-023-02298-8

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