The safety of current treatment options for advanced esophageal cancer after first-line chemotherapy

Abstract

The prognosis of advanced esophageal cancer (EC) remains poor, and few effective agents are available. For advanced EC patients, a combination of platinum and fluoropyrimidine is recognized as the standard first-line treatment. After first-line treatment, taxane or irinotecan has been used. Based on the KEYNOTE-181 and the ATTRACTION-3 trials, immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab appear to prolong survival, compared with cytotoxic agents, as second-line treatments for advanced EC patients. In addition, ICIs have different safety profiles than conventional cytotoxic agents. Herein, we discuss the differences in the safety profiles of cytotoxic agents and ICIs for the treatment of advanced EC patients after first-line chemotherapy.ICIs as a second-line treatment are tolerable in advanced EC patients. Although infrequent, ICIs can cause immune-related adverse events that are sometimes fatal. Therefore, regular monitoring of physical and laboratory examinations is needed during and after the administration of ICIs. As the major toxicities of taxane are neutropenia and neuropathy, while those of irinotecan are neutropenia and diarrhea, appropriate supportive care or dose modification may be needed for individual patients. ICI-containing treatments have been developed not only as second-line treatments, but also as first-line treatments or for use in perioperative settings; thus, particular attention with regard to immune-related toxicities is needed.

Case Report: First-Line Immunotherapy for Esophageal Squamous Carcinoma Combined With Hypopharyngeal Squamous Carcinoma Yields Sustained Survival Benefit

“…At present, the first-line standard treatment is still based on fluorouracil combined with platinum-based chemotherapy, which has low overall efficiency and is prone to drug resistance after first-line chemotherapy and leads to disease progression. The publication of the KEYNOTE-181 and ATTRACTION-3 studies suggested that after failure of first-line chemotherapy in patients with esophageal squamous cancer, second-line immunotherapy has a significant overall survival (OS) benefit over chemotherapy, and based on this, the United States Food and Drug Administration (FDA) approved PD-1 blockade therapy pembrolizumab and nivolumab for second-line treatment of advanced esophageal squamous cancer ( 7 , 8 ).Given the clear survival benefit achieved with PD-1 in second-line treatment of esophageal squamous carcinoma, the subsequent KEYNOTE-590 study of PD-1 inhibitor pembrolizumab in combination with chemotherapy versus placebo in combination with chemotherapy in first-line use in advanced esophageal squamous carcinoma also confirmed a clear OS benefit of immunotherapy ( 9 ), suggesting that PD-1 in combination with chemotherapy is expected to be the first-line standard of care. Similarly, in head and neck squamous carcinoma, KEYNOTE-048 ( 10 ), and the subsequent CheckMate 141 and KEYNOTE-040 studies have demonstrated a significant OS benefit of second-line application of the immune checkpoint inhibitor PD-1 (either pembrolizumab or nivolumab) over standard therapy in metastatic or recurrent head and neck squamous carcinoma ( 11 ).…”

Targeted Photodynamic Diagnosis and Therapy for Esophageal Cancer: Potential Role of Functionalized Nanomedicine

“…Palliative chemotherapy is often administered to patients with advanced-stage cancer. The standard chemotherapy agents for esophageal cancer include cisplatin, 5-fluorouracil, doxorubicin, capecitabine, docetaxel, irinotecan, oxaliplatin, paclitaxel, trifluridine-tripiracil, entrectinib, labrotrectinib, capecitabine, carboplatin, and leucovorin [12,13]. These drugs are usually given in combinations to improve their efficacies.…”

“…Early-stage cancer treated with chemotherapy has shown improved survival rates, particularly in combination with radiation, while a poor prognosis is observed in advanced-stage esophageal cancer [15,16]. The continuous usage of the chemotherapeutic agent is characterized by dose-limiting cytotoxicity; drug resistance; and other adverse effects such as neuropathy, neutropenia, pneumonitis, bradycardia myelosuppression, thereby limiting the extensive use of these agents [13].…”

Regional Chemotherapy Is a Valuable Second-Line Approach in Metastatic Esophageal Cancer after Failure to First-Line Palliative Treatment

“…Approximately ≥50% of the patients are diagnosed with stage IV disease and recurrence after primary curative intended therapy is also common. Hence the overall five-year survival rate of recurrent or metastatic disease remains below 5% [ 1 , 2 , 3 , 4 , 5 ].…”

“…Unfortunately, recommendations for the management of recurrent and metastatic disease are scare even in the national and oncological society guidelines [ 6 , 7 , 8 ]. Although within the last few years many trials have been conducted such as Keynote-181 and ATTRACTION-3 trial as well as phase III studies with irinotecan, docetaxel and Ramucirumab, the overall outcome remains highly unsatisfactory with ≤10 months of survival in patients failing to respond to first-line treatment [ 4 , 9 , 10 , 11 ]. This is even of more concern taking the quality of life (QoL) and required duration of therapy into consideration.…”