Progress in second-line antibody therapies for advanced esophageal squamous cell carcinoma.

INTRODUCTION: The prognosis of advanced esophageal squamous cell carcinoma (ESCC) is poor. Although cytotoxic drugs have been widely used in advanced ESCC, several antibody agents have recently been reported to be effective. AREAS COVERED: Nivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect. Randomized phase III trials have found these immune checkpoint inhibitors (ICIs) to be effective as second-line treatment. ATTRACTION-3, which compared nivolumab monotherapy with taxane monotherapy in patients with previously treated advanced ESCC, reported prolonged overall survival in the nivolumab group. KEYNOTE-181 found that overall survival was longer in patients with PD-L1-positive ESCC who received second-line treatment with pembrolizumab than in those who received chemotherapy. Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing. EXPERT OPINION: The standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.

[A Case of Fournier's Gangrene during Second-Line IRIS plus Bevacizumab Chemotherapy for Rectal and Anal Canal Cancer].

A 52-year-old man diagnosed with Stage ⅢA rectal and anal canal cancer underwent abdominal perineal resection using Miles's method. Two years later, local recurrence and lung metastases were detected using contrasted CT imaging. First-line chemotherapy of XELOX was administered for 4 months until the disease progressed and lung metastases developed. After 4 courses of second-line IRIS plus bevacizumab chemotherapy, fever and swelling of the right buttock appeared; he visited and was admitted to our hospital. A CT scan revealed a pelvic abscess which resulted in septic shock. Swelling and pain extended to the right scrotum, and acute necrotizing fasciitis was suspected, and emergency surgery was performed. An incision was made from the right buttock to the right scrotum, bloody purulent drainage with a foul odor was observed, and a diagnosis of Fournier's gangrene was made. Although typical CT findings such as emphysema due to gas-producing bacteria were not observed in this case, early diagnosis and intervention of systemic management including early surgical drainage and operation were effective. For pelvic infections occurring during bevacizumab chemotherapy, Fournier's gangrene should considered for differential diagnosis, even if CT findings are atypical.

[A Case of an Advanced Intrahepatic Cholangiocarcinoma Effectively Treated by Conversion Surgery after Neoadjuvant Chemotherapy of Gemcitabine, Cisplatin and S-1].

A 61-year-old male suffered from intrahepatic cholangiocarcinoma in S7 lesion(90 mm diameter), diagnosed by hepatic tumor biopsy. As PET-CT showed para-aortic lymph node metastasis(cT3N1M1, cStage ⅣB), and judged to be unresectable, he received neoadjuvant chemotherapy of gemcitabine, cisplatin, and S-1(GCS). After 7 courses of GCS, CT showed partial response of the primary tumor and PET-CT showed decreased accumulation of FDG at para-aortic lymph node. Resectability was reexamined and the patient underwent S7 extended subsegmentectomy as conversion surgery. Furthermore, after the surgery, he received adjuvant chemotherapy of S-1 for 6 months, and he remained relapse-free for the next 2 years. Cholangiocarcinoma is one of the most poorly prognosed type cancer. Conversion surgery for unresectable intrahepatic cholangiocarcinoma is frequently reported, but there are still few reports of GCS as neoadjuvant chemotherapy. Here, we report a case of unresectable intrahepatic cholangiocarcinoma that was successfully treated with GCS and underwent conversion surgery.

[A Case of Advanced Esophageal Cancer Discovered Due to Suffocation, Which Was Invasive to the Trachea and Internal Carotid Artery and Treated by Chemotherapy].

A 51-year-old male presented with dyspnea due to upper airway obstruction. We decided to perform a cricothyroidotomy due to difficulty in performing orotracheal intubation. A CT scan revealed a massive tumor infiltrating into the right side of the neck, which penetrated the internal carotid artery. An upper gastrointestinal tract endoscopy was performed, and the patient was diagnosed with advanced esophageal cancer(stage Ⅳ, cT4N4M0). We initiated palliative chemotherapy of FOLFOX as first-line chemotherapy. After the fourth course, the patient was evaluated as having progressive disease(PD)due to regrowth of lymph node metastasis around the lower esophagus. Although we changed the treatment to nivolumab as second-line chemotherapy, there was a gradual exacerbation of airway obstruction, and the head and upper limb edema emerged due to superior vena cava syndrome. After the first course of nivolumab, we diagnosed the patient as having clinically PD. After the first course of docetaxel(DTX)as third-line chemotherapy, he suddenly died of massive hemorrhage caused by the intubation tube on day 136. Airway management is difficult to perform in patients with a poor response to chemotherapy due to obstruction by a tumor. On the other hand, excessive response to chemotherapy is also associated with a risk of massive hemorrhage due to arterial perforation, as observed in this case.

[A Case of Recurrent Premenopausal Hormone Receptor Positive Breast Cancer with Liver, Lung and Bone Metastasis Successfully Treated with Endocrine Therapy].

Here we report a 48-year-old female with recurrent breast cancer. She had received chest muscle-conserving mastectomy and lymph node dissection at another hospital, diagnosed as pStage ⅡB, T2N1M0 premenopausal left endocrine positive/ HER2 negative breast cancer at the age of 45. Although postoperative adjuvant therapy was started with LH-RH agonist plus tamoxifen, and chest radiation, tamoxifen therapy was intolerantly discontinued due to severe adverse events of hot flash after 1 year later. Three years later, she presented with back pain and was referred to our hospital. As PET-CT revealed recurrence of multiple bone and lung metastases and solitary liver metastasis which did not seem to be life-threatening, palliative radiation therapy and endocrine therapy with leuprorelin and anastrozole(LA)were started. Eighteen months later, PET-CT showed complete disappearance of liver and lung metastases and remarkable regression of bone metastases except for the right sciatic bone. LA therapy could be maintained for a total of 30 months until metastatic recurrence on liver and bone emerged. LA endocrine therapy may be effective for patients with premenopausal hormone-positive breast cancer even if the difficult situation such as tamoxifen intolerance.