Hypothyroidism and hypopituitarism as immune-related adverse events due to lenvatinib plus pembrolizumab therapy in the immediate postoperative period after laparoscopic hepatectomy for liver metastases from gastric cancer: a case report

Abstract

Background Immune checkpoint inhibitors (ICIs) are emerging agents used for the treatment of various malignant tumors. As ICIs are generally used for unresectable malignant tumors, there have been only a few reports of patients who underwent surgery after receiving these drugs. Therefore, it remains unclear how immune-related adverse events (irAEs) affect the postoperative course. Here, we report a patient with advanced gastric cancer who underwent laparoscopic hepatectomy for liver metastases after an objective response with lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism as irAEs in the immediate postoperative period. Case presentation A 73-year-old man had undergone total gastrectomy for pT4aN2M0 gastric cancer followed by adjuvant chemotherapy with S-1 and docetaxel, and developed liver metastases in segments 6 and 7. He was enrolled in phase 2 clinical trial of lenvatinib plus pembrolizumab. He continuously achieved a partial response with the study treatment, and the liver metastases were decreased in size on imaging. The tumors were judged to be resectable and the patient underwent laparoscopic partial hepatectomy for segments 6 and 7. From the 1st postoperative day, the patient continuously presented with fever and general fatigue, and his fasting blood glucose level remained slightly lower than that before the surgery. On the 4th postoperative day, laboratory examination revealed hypothyroidism and hypopituitarism, which were suspected to be irAE caused by lenvatinib plus pembrolizumab after surgery. He received hydrocortisone first, followed by levothyroxine after adrenal insufficiency was recovered. Subsequently, his fever, general fatigue, and any abnormality regarding fasting blood glucose level resolved, and he was discharged on the 12th postoperative day. After discharge, his laboratory data for thyroid and pituitary function remained stable while receiving hydrocortisone and levothyroxine without recurrence of gastric cancer. Conclusion We present a case of laparoscopic hepatectomy after receiving lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism after surgery. Regarding surgery after ICI therapy, it is important to recognize that irAEs might occur in the postoperative period.

Construction and evaluation of clinical prediction model for immunotherapy-related adverse events and clinical benefit in cancer patients receiving immune checkpoint inhibitors based on serum cytokine levels

“…It is well known that patients who respond to ICI tend to develop irAEs (5). Kimimasa present a case of laparoscopic hepatectomy after receiving lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism after surgery, the patient treated with ICIs and responded effectively to ICI therapy before surgery (21). We need to explore whether liver metastasis is associated with the occurrence of irAEs.…”

Construction and Evaluation of Clinical Prediction Model for Immunotherapy-related Adverse Events and Clinical Benefit in Cancer Patients Receiving Immune Checkpoint Inhibitors Based on Serum Cytokine Levels

“…It is established that patients who respond to ICI tend to develop irAEs 5 . Kimimasa presented a case of laparoscopic hepatectomy after receiving lenvatinib plus pembrolizumab, in which the patient developed hypothyroidism and hypopituitarism after surgery; the patient was treated with ICIs and responded effectively to ICI therapy before surgery 21 . The association between liver metastasis and occurrence of irAEs needs to be explored further.…”

Multi‐organs perioperative immune‐related adverse events and postoperative bronchial anastomotic fistula in a patient receiving neoadjuvant immunotherapy with NSCLC

“…However, in that case, the patient was misdiagnosed as advanced lung cancer instead of resectable lung cancer. Sasaki et al 23 reported a case of laparoscopic hepatectomy after receiving lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism after surgery. Regarding surgery after neoadjuvant chemoimmunotherapy, it is essential to recognize that irAEs might occur in the postoperative period.…”