Small cell lung cancer - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main SCLC page for regimens that include active anticancer treatment.
=Limited stage, consolidation after upfront therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Jett et al. 1994 (NCCTG 86-20-51)	1987-1990 	Phase 3 (C)	IFN gamma 	Did not meet primary endpoint of OS
Kelly et al. 1995 (SWOG 8812) 	1989-1991 	Phase 3 (C)	IFN alfa-2a	Did not meet primary endpoint of OS
Giaccone et al. 2005 (Silva) 	1998-2002 	Phase 3 (C)	Bec2 & BCG 	Did not meet primary endpoint of OS
No further treatment.
====Preceding treatment====
*Definitive chemoradiotherapy
===References===
# NCCTG 86-20-51: Jett JR, Maksymiuk AW, Su JQ, Mailliard JA, Krook JE, Tschetter LK, Kardinal CG, Twito DI, Levitt R, Gerstner JB. Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer. J Clin Oncol. 1994 Nov;12(11):2321-6. link to original article EuroPMC
# SWOG 8812: Kelly K, Crowley JJ, Bunn PA Jr, Hazuka MB, Beasley K, Upchurch C, Weiss GR, Hicks WJ, Gandara DR, Rivkin S, Livingston R. Role of recombinant interferon alfa-2a maintenance in patients with limited-stage small-cell lung cancer responding to concurrent chemoradiation: a Southwest Oncology Group study. J Clin Oncol. 1995 Dec;13(12):2924-30. link to original article EuroPMC
# Silva: Giaccone G, Debruyne C, Felip E, Chapman PB, Grant SC, Millward M, Thiberville L, D'addario G, Coens C, Rome LS, Zatloukal P, Masso O, Legrand C; EORTC. Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study). J Clin Oncol. 2005 Oct 1;23(28):6854-64. link to original article EuroPMC NCT00037713
==Placebo==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Cheng et al. 2024 (ADRIATIC) 	2018-09-28 to 2021-08-18	Phase 3 (C)	1. Durvalumab 	Seems to have shorter PFS/OS
Cheng et al. 2024 (ADRIATIC) 	2018-09-28 to 2021-08-18	Phase 3 (C)	2. Durvalumab & Tremelimumab 	In progress
Awaiting publication (KEYLYNK-013)	2020-ongoing 	Phase 3 (C)	1. Pembrolizumab2. Olaparib & Pembrolizumab	In progress
No further antineoplastic treatment.
====Preceding treatment====
*ADRIATIC: Definitive chemoradiotherapy
===References===
#ADRIATIC: Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, Zenke Y, Lee KH, Wang Q, Navarro A, Bernabe R, Buchmeier EL, Chang JW, Shiraishi Y, Goksu SS, Badzio A, Shi A, Daniel DB, Hoa NTT, Zemanova M, Mann H, Gowda H, Jiang H, Senan S; ADRIATIC Investigators. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med. 2024 Oct 10;391(14):1313-1327. Epub 2024 Sep 13. link to original article EuroPMC NCT03703297
#KEYLYNK-013: NCT04624204
=Extensive stage, maintenance after first-line therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Jett et al. 1994 (NCCTG 86-20-51) 	1987-1990 	Phase 3 (C) 	IFN gamma 	Did not meet primary endpoint of OS
van Zandwijk et al. 1997 (EORTC 0883)	1989-1993 	Phase 3 (C) 	IFN gamma 	Did not meet primary endpoint of OS
Hanna et al. 2002 	1993-1998 	Phase 3 (C) 	Etoposide 	Might have shorter OS
Schiller et al. 2001 (ECOG E7593) 	1995-1999 	Phase 3 (C) 	Topotecan 	Did not meet primary endpoint of OS50%
Ready et al. 2015 (CALGB 30504) 	2007-2011 	Randomized Phase 2 (C)	Sunitinib 	Seems to have shorter PFSMedian PFS: 2.1 vs 3.7 mo(HR 1.61, 95% CI 1.02-2.63)
Santo et al. 2019 (G04.2011) 	2012-2016 	Phase 3 (C) 	Lanreotide	Did not meet primary endpoint of PFSMedian PFS: 2.3 vs 3.6 mo(HR 1.51, 95% CI 0.90-2.50)
No further treatment.
====Biomarker eligibility criteria====
*G04.2011: Somatostatin receptor positivity at diagnosis
====Preceding treatment====
*ECOG E7593: First-line Cisplatin & Etoposide x 4
*CALGB 30504: First-line Carboplatin & Etoposide or Cisplatin & Etoposide x 4 to 6 cycles
*G04.2011: First-line Carboplatin & Etoposide or Cisplatin & Etoposide
===References===
# NCCTG 86-20-51: Jett JR, Maksymiuk AW, Su JQ, Mailliard JA, Krook JE, Tschetter LK, Kardinal CG, Twito DI, Levitt R, Gerstner JB. Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer. J Clin Oncol. 1994 Nov;12(11):2321-6. link to original article EuroPMC
# EORTC 0883: van Zandwijk N, Groen HJ, Postmus PE, Burghouts JT, ten Velde GP, Ardizzoni A, Smith IE, Baas P, Sahmoud T, Kirkpatrick A, Dalesio O, Giaccone G; EORTC Lung Cancer Cooperative Group. Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer: a randomised phase III study of the EORTC Lung Cancer Cooperative Group. Eur J Cancer. 1997 Oct;33(11):1759-66. link to original article EuroPMC
# ECOG E7593: Schiller JH, Adak S, Cella D, DeVore RF 3rd, Johnson DH. Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Apr 15;19(8):2114-22. link to original article EuroPMC
# Hanna NH, Sandier AB, Loehrer PJ Sr, Ansari R, Jung SH, Lane K, Einhorn LH. Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer: a Hoosier Oncology Group randomized study. Ann Oncol. 2002 Jan;13(1):95-102. link to original article EuroPMC
# CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article EuroPMC NCT00453154
# G04.2011: Santo A, Pilotto S, Galetta D, Grossi F, Fasola G, Romano G, Bonanno L, Bearz A, Papi M, Roca E, Catino A, Follador A, Rijavec E, Genova C, Petrillo P, Favaretto A, Giannone L, Milella M, Tortora G, Giannarelli D, Bria E; Italian association FONICAP (Operative National Interdisciplinary Force against Lung Cancer). Maintenance with lanreotide in small-cell lung cancer expressing somatostatine receptors: A multicenter, randomized, phase 3 trial. Lung Cancer. 2019 Aug;134:121-126. Epub 2019 Jun 11. link to original article EuroPMC EudraCT 2011-005730-20
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Shepherd et al. 2002 (NCIC-CTG BR.12)	1997-2000 	Phase 3 (C)	Marimastat 	Did not meet primary endpoint of OS
Owonikoko et al. 2021 (CheckMate 451)	2015-2018 	Phase 3 (C)	1. Ipilimumab & Nivolumab	Did not meet primary endpoint of OSMedian OS: 9.6 vs 9.2 mo(HR 1.09, 95% CI 0.89-1.33)
Owonikoko et al. 2021 (CheckMate 451)	2015-2018 	Phase 3 (C)	2. Nivolumab 	Might have shorter OSMedian OS: 9.6 vs 10.4 mo(HR 1.19, 95% CI 0.98-1.45)
Johnson et al. 2021 (MERU) 	2017-2019 	Phase 3 (C)	Rovalpituzumab tesirine 	Did not meet primary endpoint of OS
Ai et al. 2021 (ZL-2306-005) 	2018-2020 	Phase 3 (C)	Niraparib 	Did not meet primary endpoint of OSMedian OS: 11.4 vs 9.9 mo(HR 0.97, 95% CI 0.58-1.61)
No further antineoplastic treatment.
====Preceding treatment====
*NCIC-CTG BR.12: First-line combination chemotherapy x 4, with PR/CR
*CheckMate 451: First-line platinum-based chemotherapy x 3 to 4
===References===
# NCIC-CTG BR.12: Shepherd FA, Giaccone G, Seymour L, Debruyne C, Bezjak A, Hirsh V, Smylie M, Rubin S, Martins H, Lamont A, Krzakowski M, Sadura A, Zee B; NCIC-CTG; EORTC. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organisation for Research and Treatment of Cancer. J Clin Oncol. 2002 Nov 15;20(22):4434-9. link to original article EuroPMC NCT00003011
# CheckMate 451: Owonikoko TK, Park K, Govindan R, Ready N, Reck M, Peters S, Dakhil SR, Navarro A, Rodríguez-Cid J, Schenker M, Lee JS, Gutierrez V, Percent I, Morgensztern D, Barrios CH, Greillier L, Baka S, Patel M, Lin WH, Selvaggi G, Baudelet C, Baden J, Pandya D, Doshi P, Kim HR. Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451. J Clin Oncol. 2021 Apr 20;39(12):1349-1359. Epub 2021 Mar 8. link to original article link to PMC article EuroPMC NCT02538666
# ZL-2306-005: Ai X, Pan Y, Shi J, Yang N, Liu C, Zhou J, Zhang X, Dong X, He J, Li X, Chen G, Li X, Zhang H, Liao W, Zhang Y, Ma Z, Jiang L, Cui J, Hu C, Wang W, Huang C, Zhao J, Ding C, Hu X, Wang K, Gao B, Song Y, Liu X, Xiong J, Liu A, Li J, Liu Z, Li Y, Wang M, Zhang B, Zhang D, Lu S. Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study. J Thorac Oncol. 2021 Aug;16(8):1403-1414. Epub 2021 Apr 26. link to original article EuroPMC NCT03516084
# MERU: Johnson ML, Zvirbule Z, Laktionov K, Helland A, Cho BC, Gutierrez V, Colinet B, Lena H, Wolf M, Gottfried M, Okamoto I, van der Leest C, Rich P, Hung JY, Appenzeller C, Sun Z, Maag D, Luo Y, Nickner C, Vajikova A, Komarnitsky P, Bar J. Rovalpituzumab Tesirine as a Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With Extensive-Stage-SCLC: Results From the Phase 3 MERU Study. J Thorac Oncol. 2021 Sep;16(9):1570-1581. Epub 2021 Apr 3. link to original article EuroPMC NCT03033511
=Relapsed or refractory disease=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
O'Brien et al. 2006 (GSK 104864/478)	2000-2004 	Phase 3 (C)	Oral topotecan	Seems to have shorter OS
No active antineoplastic treatment.
===References===
# GSK 104864/478: O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. link to original article EuroPMC NCT00276276
Category:Small cell lung cancer regimens
Category:Disease-specific pages
Category:Lung cancers
Category:Null regimens