Abstract
Esophageal cancer (EC) is relatively frequent and highly lethal cancer, being the sixth most common cause of cancer death worldwide. The progressive approvals of immunotherapy as first-line and second-line treatment options have paved the way for an evolving new approach to the treatment of this disease. Management of esophageal cancer is challenging and requires a multimodality approach. Treatment options include surgery, chemoradiotherapy and, recently, immunotherapy. The newest guidelines and FDA approvals regarding immunotherapy for esophageal cancer are reviewed here.
Plain language summary
Esophageal cancer is a malignant tumor that affects the cells in the esophagus. To treat this condition, doctors may use surgery, radiation therapy, chemotherapy and immunotherapy. Depending on the characteristics of the tumor and the medical history of the patient, these treatments may be used alone or in combination to optimize their effects. Immunotherapy is a treatment that aims to stimulate the immune defenses of the body against cancerous cells. Recently, it has proven to be very effective in the management of esophageal cancer, with very favorable results. It is now becoming the standard of care in the management of this disease.
Papers of special note have been highlighted as: •• of considerable interest
References
- 1. . The epidemic of oesophageal carcinoma: where are we now? Cancer Epidemiol. 41, 88–95 (2016).
- 2. . Epidemiology and risk factors for gastroesophageal junction tumors: understanding the rising incidence of this disease. Semin. Radiat. Oncol. 23(1), 3–9 (2013).
- 3. Esophageal cancer clinical presentation: trends in the last 3 decades in a large Italian series. Ann. Surg. 267(1), 99–104 (2018).
- 4. Worldwide Esophageal Cancer Collaboration: clinical staging data. Dis. Esophagus 29(7), 707–714 (2016).
- 5. Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline. J. Clin. Oncol. 38(23), 2677–2694 (2020).
- 6. NCCN Guidelines for Patients: Esophageal Cancer (2022). www.nccn.org/patients/guidelines/content/PDF/esophageal-patient.pdf
- 7. Preoperative chemoradiotherapy for esophageal or junctional cancer. N. Engl. J. Med. 366(22), 2074–2084 (2012).
- 8. Comparing paclitaxel plus fluorouracil versus cisplatin plus fluorouracil in chemoradiotherapy for locally advanced esophageal squamous cell cancer: a randomized, multicenter, Phase III clinical trial. J. Clin. Oncol. 37(20), 1695–1703 (2019).
- 9. . Chemoradiotherapy versus chemoradiotherapy plus surgery for esophageal cancer. Cochrane Database Syst. Rev. 8, CD010511 (2017).
- 10. Single-institution retrospective comparison of preoperative versus definitive chemoradiotherapy for adenocarcinoma of the esophagus. Ann. Surg. Oncol. 21(12), 3744–3750 (2014).
- 11. Preoperative nomogram to risk stratify patients for the benefit of trimodality therapy in esophageal adenocarcinoma. Ann. Surg. Oncol. 25(6), 1598–1607 (2018).
- 12. . Salvage systemic therapy for advanced gastric and oesophago-gastric junction adenocarcinoma. Cochrane Database Syst. Rev. 11, CD012078 (2020).
- 13. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer. Int. J. Radiat. Oncol. Biol. Phys. 67(2), 385–388 (2007).
- 14. The value of palliative gastrectomy in gastric cancer with distant metastasis. Ann. Surg. Oncol. 19(4), 1231–1239 (2012).
- 15. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N. Engl. J. Med. 384(13), 1191–1203 (2021). •• This article describes the trial that led to the US FDA approval of nivolumab for patients with completely resected esophageal cancer with residual pathologic disease who previously received neoadjuvant chemoradiotherapy (trimodality therapy)
- 16. . Locally advanced esophageal carcinoma guideline expert panel. immunotherapy in patients with locally advanced esophageal carcinoma: ASCO treatment of locally advanced esophageal carcinoma guideline rapid recommendation update. J. Clin. Oncol. 39(28), 3182–3184 (2021).
- 17. KEYNOTE-590: phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 15(10), 1057–1066 (2019). •• This article describes the trial that led to the FDA approval of pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal cancer who are not candidates for surgery or definitive chemoradiotherapy.
- 18. Nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/oesophageal adenocarcinoma (CheckMate 649): a multicentre, randomised, open-label, Phase 3 trial. Lancet 398(10294), 27–40 (2021). •• This article describes the trial that led to the FDA approval of nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced or metastatic gastroesophageal junction cancer and esophageal adenocarcinoma.
- 19. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 20(11), 1506–1517 (2019). •• This article describes the trial that led to the FDA approval of nivolumab for patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma, after prior fluoropyrimidine and platinum-based chemotherapy
- 20. Combination therapy of established tumors by antibodies targeting immune activating and suppressing molecules. J. Immunol. 184(10), 5493–5501 (2010).
- 21. KEYNOTE-585: phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer. Future Oncol. 15(9), 943–952 (2019).
- 22. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol. 17(10), 1143–1153 (2021).
- 23. Third-line nivolumab monotherapy in recurrent SCLC: CheckMate 032. J. Thorac. Oncol. 14(2), 237–244 (2019).
- 24. Combination of ipilimumab and nivolumab in cancers: from clinical practice to ongoing clinical trials. Int. J. Mol. Sci. 21(12), E4427 (2020).
- 25. Safety and effectiveness of pembrolizumab combined with paclitaxel and cisplatin as neoadjuvant therapy followed by surgery for locally advanced resectable (stage III) esophageal squamous cell carcinoma: a study protocol for a prospective, single-arm, single-center, open-label, Phase-II trial (Keystone-001). Ann. Transl. Med. 10(4), 229 (2022).
- 26. Pembrolizumab combined with neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy followed by surgery for locally advanced oesophageal squamous cell carcinoma: protocol for a multicentre, prospective, randomized-controlled, Phase III clinical study (Keystone-002). Front. Oncol. 12, 831345 (2022).