On October 16th, 2018, a 54-year-old married female patient, who was postmenopausal for 7 years and had 2 children, initially visited our hospital due to a pelvic mass accidentally found for 2 weeks. She underwent a resection of the left temporal skin basal cell carcinoma in September 2018, and her father died of brain metastases from lung cancer. Except for those, no other notable medical histories were present. Results of physical examinations were generally normal. Transvaginal ultrasound in our hospital showed a heterogeneous hypoechoic mass with a size of 11.9x9.3 x 9.0 cm in the pelvic cavity, and an ultrasound-guided needle biopsy of the mass was performed. The carbohydrate antigen 125 (CA125) is 517.3 U/mL. The patient was primarily diagnosed with ovarian cancer based on a pathological report of intrapelvic adenocarcinoma and results of immunohistochemistry. The results showed that ER(+), PMS2(+80%), MLH1(+80%), MSH2(+90%), MSH6(+90%), PR(-), P16(+), WT-1(+), p53(+90%), Ki-67(+80%), HER-1(EGFR)(+), HER-2(1+), CDX-2(small focal+), Villin(-).
On admission, gynecological examination suggested that the pelvic range of motion was poor and closely related to the rectum, and the risk of rectal injury was greater, and there was ascites, it was difficult to achieve R0 in surgery. After adequate evaluation and discussion, the patient was given two-course neoadjuvant chemotherapy with paclitaxel and cisplatin (TP). The neoadjuvant treatment time was October 30, 2018, and November 29, 2018 respectively. On January 4, 2019, the patient underwent open abdominal cytoreductive surgery for ovarian cancer. Then she was diagnosed with stage IIIC moderately differentiated ovarian endometrioid adenocarcinoma based on postoperative pathology. The patient received satisfactory cytoreductive surgery and achieved R0. From January 13, 2019, to June 20, 2019, the patient was given six-course TP chemotherapy after surgery. Due to tumor recurrence suggested by imaging, bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, was combined since the 4th course of TP chemotherapy. At the end of treatment in June 2019, the ultrasound showed a hypoechoic nodule with a size of about 1.4 x 2.1 x 1.6 cm above the vagina. Follow-up regular reexaminations detected a slow growth of the vaginal hypoechoic nodule to 3.2 x 2.6 x 3.3 cm and new multiple small nodules in the pelvic cavity. In combination with biopsy pathology, it was considered to be tumor recurrence with metastasis, and the disease progressed. The patient was diagnosed with PROC and unable to be treated promptly due to coronavirus outbreak, no maintenance treatment and pelvic lesions persisted and progressed.
On August 9, 2020, the patient was enrolled in a phase II study for PROC patients (ChiCTR1900027114) and treated with combination treatment of fuzuloparib (100mg PO BID), apatinib (250mg PO QD), and camrelizumab (200mg IV Q3W) for every 3-week cycle. From August 9, 2020, to November 23, 2021, twenty-one cycles of therapy have been administered. CT scans revealed a partial response. At baseline, the diameter of target lesions at the vaginal stump and in front of rectum was 44 mm (Figure 1), and multiple lymph nodes below 8 mm in the internal iliac vessel region were observed for non-target lesions (Figure 2). After the 4th cycle of treatment, non-target lesions disappeared and did not recur (Figure 3). At the end of the 11th cycle, the diameter of target lesions reduced to 3.9 mm without significant change thereafter (Figure 4). Target lesions sharply decrease by 91.14%. No new lesions were found.
The incidence of grade 3 and above adverse reactions was 0. After the 4th cycle of treatment (November 5, 2020), grade 2 hypothyroidism gradually occurred. The main symptoms included serum-free T4 level gradually decreased to a minimum of 4.63 pmol/L, and serum thyroid-stimulating hormone level gradually increased to a maximum of 108.15 mU/L, accompanied by fatigue, weight gain, ECG ST-T changes, and other symptoms. The patient was given regular oral administration of levothyroxine sodium tablets (75ug QD) till now. Related symptoms were gradually relieved with good control. Reexamination of thyroid function was within the normal range. Another adverse reaction was a grade I red blood cell count decreased, which was fluctuating between 3.38 x 1012/L and 3.8 x 1012/L. The patient had no subjective symptoms and did not require clinical intervention. The hemoglobin, white blood cell count, and neutrophil count were within the normal range. The above adverse reactions were considered related to anti-PD-1 antibody and PARP inhibitor drugs, rather than the new adverse reactions due to the triplet combination therapy.
At baseline, the patient's CA125 level was 33.35 U/mL. After the 2nd cycle of treatment, CA125 level decreased to 4.78 U/mL, and was within the normal range on subsequent visits. Moreover, the patient underwent genetic testing and additional immunohistochemical tests during treatment of triplet combination. Genetic testing revealed BRCA1 (+), which was performed on September 22, 2021. Immunohistochemistry indicated PD-L1 (SP263), TC < 1%, CPS: 2, MLH1 (+>90%), MSH2 (+>90%), MSH6 (+>90%), and PMS2 (+>90%), which was performed on October 10, 2021.
The patient is still receiving triplet combination treatment with stable vital signs, significantly improved mental status, good appetite, and weight increased by 3 kg than before. Quality of life has been greatly improved, including significantly improved physical condition and mental and psychological status compared with those before participating in the clinical trial. The patient is self-sufficient in daily living with the eastern cooperative oncology group performance status (ECOG PS) of 2.