Advanced Oesophageal Cancer: A Step Forward in Chemotherapy-Free Treatment

By Maham Zaman, Efrah Ashraf, Vikash Kumar Karmani

Affiliations

1. Department of Internal Medicine, Quaid-e-Azam Medical College, Bahawalpur, Pakistan

doi: 10.29271/jcpsp.2024.10.1267

Sir,

Oesophageal cancer (EC) is a major global health issue, ranking seventh in incidence and the sixth foremost cause of cancer-associated mortality worldwide in 2020.¹ Recent data show a concerning increase in the incidence and mortality of EC, with Asia contributing to nearly 80% of the global cases. This increase is significantly straining healthcare systems, especially in nations with lower and moderate incomes.² Cytotoxic chemotherapy, either as a stand-alone treatment or in conjunction with immune checkpoint inhibitors (ICIs), is the preferred initial therapy for advanced or metastatic unresectable solid tumours of the gastrointestinal (GI) tract.³ For individuals with advanced gastroesophageal junction cancers (GEJCs), chemotherapy is often ineffective with most patients surviving less than a year after treatment. Additionally, they must endure severe side effects. Japanese patients with advanced EC typically have an average survival of only 8.1 months following chemotherapy. It is crucial to find more effective and tolerable treatment options that are more effective and easier to tolerate.⁴

A recent clinical trial conducted solely in China has introduced a revolutionary regimen devoid of chemotherapy.³ It combines toripalimab, a PD-1 inhibitor, with surufatinib, a multi-targeted tyrosine kinase inhibitor (TKI), demonstrating significant anti-tumour effects alongside manageable side effects. A total of 60 patients were included in the study between 17 December 2019, and 29 January 2021: 20 with gastric cancer (GC) / GEJCs and another 20 with oesophageal squamous cell carcinomas (ESCCs). By 28 February 2023, the objective response rates were 31.6% for GC / GEJCs and 30.0% for ESCCs. The median progression-free survival was 4.1 months for GC / GEJCs and 2.7 months for ESCCs, with median overall survival recorded at 13.7 months for GC / GEJCs and 10.4 months for ESCCs.⁵

The encouraging results of the chemotherapy-free regimen, highlighted by the combination of surufatinib and toripalimab with manageable side effects, emphasise the importance of ongoing research and larger clinical trials. If subsequent trials confirm these outcomes, it could represent a significant milestone in oncology, promising better treatment options, and enhanced quality of life for patients. Nevertheless, it is essential to acknowledge the limitation that this trial was conducted exclusively on Chinese patients. To ensure the broader relevance and applicability of these promising findings, conducting additional studies across diverse global populations is imperative.
 

COMPETING  INTEREST:
The  authors  declared  no  conflict  of  interest.

AUTHORS’ CONTRIBUTION:
MZ: Conceptualised the idea, conducted the literature review, analysed and interpreted the data, and contributed to the drafting of the manuscript.
EA: Wrote the manuscript and critically revised it for important intellectual content.
VKK: Ensured the accuracy of references and final approval of the manuscript.
All authors approved the final version of the manuscript to be published.

REFERENCES

1. Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, et al. Toripali-mab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Cancer Cell 2022; 40(3):277-88. doi: 10.1016/j.ccell.2022.02.007.
2. Zhu H, Wang Z, Deng B, Mo M, Wang H, Chen K, et al. Epidemiological landscape of esophageal cancer in Asia: Results from Globocan 2020. Thoracic Cancer 2023; 14(11):992-1003. doi: 10.1111/1759-7714.14835.
3. Zhang P, Chen Z, Shi S, Li Z, Ye F, Song L, et al. Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer. Cancer Immunol Immunother 2024; 73(7):119. doi: 10.1007/s00262-024- 03677-7.
4. Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, et al. First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus 2022; 19(4):683-92. doi: 10.1007/ s10388-022-00920-x.
5. Moehler M, Xiao H, Blum HI, Elimova E, Cella D, Shitara K, et al. Health-related quality of life with nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric/gastroesophageal junction cancer or esophageal adenocarcinoma from CheckMate 649. J Clin Oncol 2023; 41(35):5388-99. doi: 10.1200/JCO.23.00170.