The emerging landscape of immune checkpoint inhibitor based clinical trials in adults with advanced rare tumors

References

• DeSantis CE, Kramer JL, Jemal A. The burden of rare cancers in the United States. CA Cancer J Clin. 2017;67:261–72.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.
   PubMed Web of Science ®Google Scholar
• Gatta G, van der Zwan JM, Casali PG, Siesling S, Dei Tos AP, Kunkler I, Otter R, Licitra L, Mallone S, Tavilla A, et al. Rare cancers are not so rare: the rare cancer burden in Europe. Eur J Cancer. 2011;47(17):2493–511. doi:10.1016/j.ejca.2011.08.008.
   PubMed Web of Science ®Google Scholar
• Greenlee RT, Goodman MT, Lynch CF, Platz CE, Havener LA, Howe HL. The occurrence of rare cancers in U.S. adults, 1995-2004. Public Health Rep. 2010;125(1):28–43. doi:10.1177/003335491012500106.
   PubMed Web of Science ®Google Scholar
• Boyd N, Dancey JE, Gilks CB, Huntsman DG. Rare cancers: a sea of opportunity. Lancet Oncol. 2016;17(2):e52–e61. doi:10.1016/S1470-2045(15)00386-1.
   PubMed Web of Science ®Google Scholar
• Billingham L, Malottki K, Steven N. Research methods to change clinical practice for patients with rare cancers. Lancet Oncol. 2016;17(2):e70–e80. doi:10.1016/S1470-2045(15)00396-4.
   PubMed Web of Science ®Google Scholar
• Mittra A, Moscow JA. Future approaches to precision oncology-based clinical trials. Cancer J. 2019;25(4):300–04. doi:10.1097/PPO.0000000000000383.
   PubMed Web of Science ®Google Scholar
• Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8(9):1069–86. doi:10.1158/2159-8290.CD-18-0367.
   PubMed Web of Science ®Google Scholar
• Fujiwara Y, Mittra A, Naqash AR, Takebe N. A review of mechanisms of resistance to immune checkpoint inhibitors and potential strategies for therapy. Cancer Drug Resist. 2020;3:252–75.
   PubMedGoogle Scholar
• Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20. doi:10.1056/NEJMoa1500596.
   PubMed Web of Science ®Google Scholar
• FDA. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. 2017. [Accessed 2020 Oct 8 https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication.
   Google Scholar
• Subbiah V, Solit DB, Chan TA, Kurzrock R. The FDA approval of pembrolizumab for adult and pediatric patients with tumor mutational burden (TMB) ≥10: a decision centered on empowering patients and their physicians. Ann Oncol. 2020;31(9):1115–18. doi:10.1016/j.annonc.2020.07.002.
   PubMed Web of Science ®Google Scholar
• Patel SP, Othus M, Chae YK, Giles FJ, Hansel DE, Singh PP, Fontaine A, Shah MH, Kasi A, Baghdadi TA, 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 non-pancreatic neuroendocrine tumors. Clin Cancer Res. 2020;26(10):2290–96. doi:10.1158/1078-0432.CCR-19-3356.
   PubMed Web of Science ®Google Scholar
• Chae YK, Othus M, Patel SP, Zalupski M, Kasi A, Khalil M, Kalyan A, Polite B, Fenton S, Gurung S, McLeod CM, et al. Abstract 3417: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the small bowel tumor cohort. Cancer Res. 2020;80(16 Supplement):3417–3417.
   Web of Science ®Google Scholar
• Adams S, Othus M, Patel SP, Chae YK, Miller K, Chugh R, Schuetze S, Sharon E, Korde LA, Gray RJ, et al. Dual anti-CTLA-4 and anti-PD-1 blockade in metaplastic carcinoma of the breast: dart (SWOG S1609, Cohort 36). J Clin Oncol. 2020;38(15_suppl):1073–1073. doi:10.1200/JCO.2020.38.15_suppl.1073.
   Web of Science ®Google Scholar
• Wagner M, Othus M, Patel S, Ryan C, Sangal A, Powers B, Budd G, Victor A, Hsueh CT, et al. A multicentre phase II trial of ipilimumab (SWOG 1609, cohort 51) and nivolumab in metastatic or unresectable angiosarcoma. A substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors: Abstract 795. Late-Breaking Abstract Presented at Annual SITC meeting, November 2020
   Google Scholar
• Florou V, Rosenberg AE, Wieder E, Komaduri KV, Kolonias D, Uduman M, Castle JC, Buell JS, Trent JC, Wilkly BA. Angiosarcoma patients treated with immune checkpoint inhibitors: A case series of seven patients from a single institution. J Immunother Cancer. 2019 Aug 8;7(1):213.
   Web of Science ®Google Scholar
• Klein O, Kee D, Markman B, 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(17):4454–59.
   PubMed Web of Science ®Google Scholar
• Klein O, Kee D, Markman B, Michael M, Underhill CR, Carlino MS, Jackett L, Lum C, Scott CL, Nagrial A, Behren A, et al. Evaluation of combination nivolumab and ipilimumab immunotherapy in patients with advanced biliary tract cancers: subgroup analysis of a Phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6(9):1405–09. doi:10.1001/jamaoncol.2020.2814.
   PubMed Web of Science ®Google Scholar
• Naing A, Meric-Bernstam F, Stephen B, Karp DD, Hajjar J, Rodon Ahnert J, Piha-Paul SA, Colen RR, Jimenez C, Raghav KP, et al. Phase 2 study of pembrolizumab in patients with advanced rare cancers. J Immunother Cancer. 2020;8(1):e000347. doi:10.1136/jitc-2019-000347.
   PubMed Web of Science ®Google Scholar
• Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10026):1405–14. doi:10.1016/S0140-6736(15)01238-6.
   PubMed Web of Science ®Google Scholar
• Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–44. doi:10.1200/JCO.2003.11.136.
   PubMed Web of Science ®Google Scholar
• Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, van Brummelen E, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):623–30.
   PubMed Web of Science ®Google Scholar
• Quispel-Janssen J, van der Noort V, de Vries JF, Zimmerman M, Lalezari F, Thunnissen E, Monkhorst K, Schouten R, Schunselaar L, Disselhorst M, et al. Programmed Death 1 blockade with nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol. 2018;13(10):1569–76. doi:10.1016/j.jtho.2018.05.038.
   PubMed Web of Science ®Google Scholar
• Hassan R, Thomas A, Nemunaitis JJ, Patel MR, Bennouna J, Chen FL, Delord J-P, Dowlati A, Kochuparambil ST, Taylor MH, et al. Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma: phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol. 2019;5(3):351–57. doi:10.1001/jamaoncol.2018.5428.
   PubMed Web of Science ®Google Scholar
• Disselhorst MJ, Quispel-Janssen J, Lalezari F, Monkhorst K, de Vries JF, van der Noort V, Harms E, Burgers S, Baas P. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019;7(3):260–70. doi:10.1016/S2213-2600(18)30420-X.
   PubMed Web of Science ®Google Scholar
• Scherpereel A, Mazieres J, Greillier L, Lantuejoul S, Dô P, Bylicki O, Monnet I, Corre R, Audigier-Valette C, Locatelli-Sanchez M, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019;20(2):239–53. doi:10.1016/S1470-2045(18)30765-4.
   PubMed Web of Science ®Google Scholar
• Fitzgerald TL, Dennis S, Kachare SD, Vohra NA, Wong JH, Zervos EE. Dramatic increase in the incidence and mortality from merkel cell carcinoma in the United States. Am Surg. 2015;81(8):802–06. doi:10.1177/000313481508100819.
   PubMed Web of Science ®Google Scholar
• Iyer JG, Blom A, Doumani R, Lewis C, Tarabadkar ES, Anderson A, Ma C, Bestick A, Parvathaneni U, Bhatia S, et al. Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma. Cancer Med. 2016;5(9):2294–301. doi:10.1002/cam4.815.
   PubMed Web of Science ®Google Scholar
• Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D’Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374–85. doi:10.1016/S1470-2045(16)30364-3.
   PubMed Web of Science ®Google Scholar
• Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D’Angelo SP, Shih KC, Lebbé C, Milella M, Brownell I, et al. Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer. 2018;6(1):7. doi:10.1186/s40425-017-0310-x.
   PubMed Web of Science ®Google Scholar
• FDA. Avelumab (BAVENCIO) 2017. [Accessed 2020, Oct 13]. https://www.fda.gov/drugs/resources-information-approved-drugs/avelumab-bavencio.
   Google Scholar
• Garcia‐Carbonero R, Marquez‐Rodas I, de la Cruz‐Merino L, Martinez‐Trufero J, Cabrera MA, Piulats JM, Capdevila J, Grande E, Martin‐Algarra S, Berrocal A, et al. Recent therapeutic advances and change in treatment paradigm of patients with merkel cell carcinoma. The Oncologist. 2019;24(10):1375–83. doi:10.1634/theoncologist.2018-0718.
   PubMed Web of Science ®Google Scholar
• Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D’Angelo S, Attia S, Riedel RF, Priebat DA, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;18(11):1493–501. doi:10.1016/S1470-2045(17)30624-1.
   PubMed Web of Science ®Google Scholar
• D’Angelo SP, Mahoney MR, Van Tine BA, Atkins J, Milhem MM, Jahagirdar BN, Antonescu CR, Horvath E, Tap WD, Schwartz GK, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol. 2018;19(3):416–26. doi:10.1016/S1470-2045(18)30006-8.
   PubMed Web of Science ®Google Scholar
• Burgess MA, Bolejack V, Schuetze S, Van Tine BA, Attia S, Riedel RF, Hu JS, Davis LE, Okuno SH, Priebat DA, et al. Clinical activity of pembrolizumab (P) in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated/pleomorphic liposarcoma (LPS): final results of SARC028 expansion cohorts. J Clin Oncol. 2019;37(15):2. doi:10.1200/JCO.2019.37.15_suppl.11015.
   Web of Science ®Google Scholar
• Dufresne A, Lesluyes T, Ménétrier-Caux C, Brahmi M, Darbo E, Toulmonde M, Italiano A, Mir O, Le Cesne A, Le Guellec S, et al. Specific immune landscapes and immune checkpoint expressions in histotypes and molecular subtypes of sarcoma. Oncoimmunology. 2020;9(1):1792036–1792036. doi:10.1080/2162402X.2020.1792036.
   PubMed Web of Science ®Google Scholar
• Petitprez F, de Reyniès A, Keung EZ, Chen TWW, Sun C-M, Calderaro J, Jeng Y-M, Hsiao L-P, Lacroix L, Bougoüin A, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577(7791):556–60. doi:10.1038/s41586-019-1906-8.
   PubMed Web of Science ®Google Scholar
• Keung EZ, Burgess M, Salazar R, Parra ER, Rodrigues-Canales J, Bolejack V, Van Tine BA, Schuetze SM, Attia S, Riedel RF, et al. Correlative Analyses of the SARC028 trial reveal an association between sarcoma-associated immune infiltrate and response to pembrolizumab. Clin Cancer Res. 2020;26(6):1258–66. doi:10.1158/1078-0432.CCR-19-1824.
   PubMed Web of Science ®Google Scholar
• Paoluzzi L, Maki RG. Diagnosis, prognosis, and treatment of alveolar soft-Part Sarcoma A Review. JAMA Oncol. 2019;5(2):254–60. doi:10.1001/jamaoncol.2018.4490.
   PubMed Web of Science ®Google Scholar
• Wilky BA, Trucco MM, Subhawong TK, Florou V, Park W, Kwon D, Wieder ED, Kolonias D, Rosenberg AE, Kerr DA, et al. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol. 2019;20(6):837–48. doi:10.1016/S1470-2045(19)30153-6.
   PubMed Web of Science ®Google Scholar
• O’Sullivan Coyne G, Moore N, Sharon E, et al. Effective treatment of alveolar soft part sarcoma with single agent atezolizumab. Paper presented at: The Connective Tissue Oncology Society (CTOS) Annual Meeting 2019; Tokyo, Japan.
   Google Scholar