Esophageal squamous cell carcinoma - null regimens

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 esophageal SCC page for regimens that include active anticancer treatment.

Neoadjuvant induction therapy

No neoadjuvant therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bosset et al. 1997	1989-1995	Phase 3 (C)	Cisplatin & RT	Did not meet primary endpoint of OS60
Boonstra et al. 2011	1989-1996	Phase 3 (C)	EP	Seems to have inferior OS
Ancona et al. 2001 (CNR-012809)	1992-1997	Phase 3 (C)	CF	Did not meet primary endpoint of OS
Lee et al. 2004	1999-2002	Phase 3 (C)	CF & RT	Did not meet primary endpoint of OS50%
Yang et al. 2018 (NEOCRTEC5010)	2007-2014	Phase 3 (C)	Cisplatin, Vinorelbine, RT	Seems to have inferior OS

Surgery as primary therapy; i.e., no induction chemotherapy or chemoradiotherapy, and no adjuvant therapy.

Subsequent treatment

• Surgery

References

1. Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, Lozach P, Ollier JC, Pavy JJ, Mercier M, Sahmoud T. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997 Jul 17;337(3):161-7. link to original article PubMed
2. CNR-012809: Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001 Jun 1;91(11):2165-74. link to original article PubMed NCT00002897
3. Lee JL, Park SI, Kim SB, Jung HY, Lee GH, Kim JH, Song HY, Cho KJ, Kim WK, Lee JS, Kim SH, Min YI. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol. 2004 Jun;15(6):947-54. link to original article PubMed
4. Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011 May 19;11:181. link to original article link to PMC article PubMed
5. NEOCRTEC5010: Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): a phase III multicenter, randomized, open-label clinical trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. Epub 2018 Aug 8. link to original article link to PMC article PubMed NCT01216527
   1. Update: Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J. Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg. 2021 Aug 1;156(8):721-729. link to original article link to PMC article PubMed

Adjuvant therapy

Observation

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ando et al. 1997 (JCOG8806)	1988-1991	Phase 3 (C)	Cisplatin & Vindesine	Did not meet primary endpoint of OS60
Ando et al. 2003 (JCOG 9204)	1992-1997	Phase 3 (C)	CF	Seems to have inferior DFS

Surgery as primary therapy; i.e., no induction chemotherapy or chemoradiotherapy, and no adjuvant therapy.

Preceding treatment

• Surgery

References

1. JCOG8806: Ando N, Iizuka T, Kakegawa T, Isono K, Watanabe H, Ide H, Tanaka O, Shinoda M, Takiyama W, Arimori M, Ishida K, Tsugane S. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study. J Thorac Cardiovasc Surg. 1997 Aug;114(2):205-9. link to original article PubMed
2. JCOG 9204: Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W, Watanabe H, Isono K, Aoyama N, Makuuchi H, Tanaka O, Yamana H, Ikeuchi S, Kabuto T, Nagai K, Shimada Y, Kinjo Y, Fukuda H; JCOG. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study--JCOG9204. J Clin Oncol. 2003 Dec 15;21(24):4592-6. link to original article PubMed

Consolidation after definitive therapy

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (SKYSCRAPER-07)	2020-2024	Phase 3 (C)	1. Atezolizumab 2. Atezolizumab & Tiragolumab	TBD if different primary endpoints of PFS/OS

No active antineoplastic treatment.

Preceding treatment

• Definitive chemoradiotherapy (not specified)

References

1. SKYSCRAPER-07: NCT04543617