Pembrolizumab in MSI-high Pancreatic Sarcomatoid Carcinoma

Case Report

Ann Hematol Oncol. 2021; 8(2): 1327.

Pembrolizumab in MSI-high Pancreatic Sarcomatoid Carcinoma

Mayrhofer K*

Department of Medical Oncology, Klinik Ottakring, Austria

*Corresponding author: Mayrhofer K, Department of Medical Oncology, Klinik Ottakring, MontleartstraΒe 37, 1160 Vienna, Austria

Received: January 03, 2021; Accepted: February 03, 2021; Published: February 10, 2021


We report the outcome of a patient with MSI-high metastatic pancreatic sarcomatoid carcinoma refractory to multiple lines of chemotherapy treated successfully with pembrolizumab.

In November 2015, our patient presented with epigastric pain leading to radiologic workup. A lesion in the pancreas as well as liver metastasis were diagnosed; liver biopsy revealed a poorly differentiated sarcomatoid carcinoma. After having received every approved chemotherapy for pancreatic cancer his disease eventually progressed so that we reached out for novel therapeutic strategies. Because of the tumor being MSI high, treatment with pembrolizumab was commenced in May 2017. Clinical response with better overall quality of life was soon reported and repeated CT scans showed an ongoing partial response leading to a near complete remission in the latest scan obtained. Adverse events during the course of therapy included immune mediated arthralgia grade 1, colitis grade 2 and pneumonitis grade 1 which were managed by administration of glucocorticoids without interruption of immunotherapy. To our knowledge, this is the first case of a patient with MSI high metastatic sarcomatoid carcinoma of the pancreas successfully treated with immunotherapy for more than three years.

Keywords: Pembrolizumab; Sarcomatoid carcinoma; Pancreatic cancer

Case Presentation

Because of epigastric pain our patient underwent abdominal ultrasound which revealed hepatic lesions as well as a tumor in the pancreas. The patient was then referred to our clinic where a Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) was performed, confirming the sonographic findings. Liver biopsy showed metastasis of a poorly differentiated Sarcomatoid Carcinoma (SC). Immunohistochemistry was unable to definitely attribute the tissue sample to a specific organ. The radiologic workup however indicated that the metastasis originated from the pancreas because of pathologic locoregional lymph nodes and a high correlation between the hepatic lesions and the pancreatic tumor in terms of radiographic characteristics. Hence, the diagnosis of a metastatic sarcomatoid pancreatic cancer was made and discussed with the patient. He presented in a good performance status, comorbidities were a well-controlled arterial hypertension and insomnia requiring oral medication. Family history was positive with his father having had pancreatic cancer, his sister breast cancer and his daughter colon cancer. With the patient’s consent, a therapy consisting of gemcitabine and albumin-bound paclitaxel was initiated in November 2015. Tolerance to therapy was very good and after 6 cycles, staging CT showed a complete remission of the malignant liver lesions and a partial remission of the primary tumor. MRI and contrast enhanced ultrasound confirmed complete disappearance of all liver metastasis. Based on these results, our tumor board recommended to pause chemotherapy, do a follow up imaging 8 weeks later and if there are no signs of disease progression, proceed to surgery of the primary tumor. Follow up imaging with CT and MRI excluded progressive disease and the patient underwent whipple resection of the pancreatic tumor. Histology revealed stage ypT3 N1 V1 L0 with necrosis of approximately 50% of the tumor tissue. The patient recovered quite well without major complications from surgery.

Due to the extraordinary response to first line chemotherapy, the decision to continue therapy postoperatively was made. After receiving another two cycles of gemcitabine and albumin-bound paclitaxel, however, disease progression in the form of appearance of new hepatic metastasis as well as retroperitoneal lymphadenopathy was evident in October 2016.

Second line chemotherapy according to the FOLFOX (folinic acid, fluorouracil, oxaliplatin) protocol was commenced in the same month. Therapy tolerance was poor with prolonged nausea and worsening performance status during the course of therapy. After the fourth application, the patient was admitted to our ward due to prolonged diarrhea, vomiting and grade 4 neutropenia. He was able to continue therapy with a reduced dose (75%) of fluorouracil afterwards. The first staging CT after 9 applications of FOLFOX showed mixed response of the liver lesions. Therapy was then switched to nanoliposomal irinotecan combined with fluorouracil in March 2017. Treatment tolerance was poor mainly caused by fatigue symptoms. Therapy had to be interrupted due to an infectious complication after two applications. Moreover, signs of clinical progression led to early restaging by CT, which confirmed progressive disease of the liver (Figure 1). The patient was now refractory to third line therapy and also unable to tolerate any further chemotherapy. In this situation, we reached out for novel therapeutic strategies. The tissue sample of the whipple resection was analysed for Microsatellite Instability (MSI) by immunohistochemistry and turned out to be MSI high. Given the extraordinary pivotal data of pembrolizumab in deficient Mismatch Repair (dMMR) gastrointestinal tumors [1-8], pembrolizumab was started after positive recommendation of our tumor board in May 2017. Following treatment initiation, the patient soon reported a better overall quality of life and less fatigue. Repeated CT scans showed an ongoing partial response and overall treatment tolerance was well. In November 2017 he developed mild generalised arthralgia probably immunotherapy associated with a prompt resolution by administration of intermediate dose glucocorticoids. Therapy hasn’t had to be interrupted and glucocorticoid dose was tapered to 7.25mg prednisolone daily. The patient achieved a long-lasting response to pembrolizumab therapy. In the further course of his disease, he was admitted to our ward in June 2019 due to pneumonia and immunotherapy associated colitis. CT scan confirmed pneumonia and also revealed mild (grade 1) signs of pneumonitis. The SC still was in near complete remission with only two small liver lesions remaining. With appropriate management consisting of antibiotics and glucocorticoids he recovered quickly and was discharged after one week. Corticosteroids were tapered to a daily dose of 1mg dexamethasone. Pembrolizumab therapy was continued afterwards and to date (December 2020) is still ongoing (Figure 2). The latest obtained CT scan in August 2020 showed a near complete remission of the liver metastasis (Figure 3).