Phase II Study of PD-1 Antibody Combined With Radiotherapy in Recurrent or Metastatic Adrenal Cortical Carcinoma
Adrenal cortical cancer is an extremely rare and highly aggressive malignancy with an incidence of 0.7-2 per million people · year and a 5-year overall survival rate of 15-44%, among which the 5-year survival rate of stage IV cortical cancer is only 13% and the prognosis is poor. Complete surgical resection is one of the most important ways to cure cortical cancer, but the surgical trauma is large, the complications are high, the postoperative recovery of patients is slow, and the tumor is difficult to achieve complete resection, and the postoperative recurrence and metastasis rate of patients is high, even for localized cortical cancer (stage I-III), the recurrence and metastasis rate is still close to 60%. Recurrent or metastatic cortical cancer is mainly treated with drugs. However, the current first-line drug therapy is only 22.3% effective, the tumor progression-free time is 5.6 months, and the serious adverse reaction rate is as high as 58.1%. The effective rate of second-line treatment with chemotherapy and targeted drugs was less than 10%, and the tumor progression-free time was only 2.8 months. The Phase II study of PD-1 monoclonal antibody in the treatment of cortical cancer showed that the treatment effective rate was 23%, and the tumor progression-free survival time was 2.1 months, which was comparable to the first-line regimen, and has been approved by the guidelines for advanced cortical cancer. Radiation therapy has high efficiency and local control rate, small side effects, and can inhibit tumor growth, relieve local pressure and pain. However, it only has a good effect on the irradiated site, and it is difficult to inhibit the progression of non-radiotherapy lesions and the generation of other new lesions. The synergistic effect of immunotherapy combined with radiation therapy for metastatic stoves has been confirmed in many solid tumors such as kidney cancer, which can improve the local control rate of solid tumors and prolong the time of tumor progressive-free. In the early stage, this research team applied PD-1 monoclonal antibody combined with radiotherapy to treat recurrent or metastatic adrenal cortical cancer in many cases after receiving first-line drug therapy regimen, which not only achieved local control of the radiotherapy focus, but also inhibited the progression of other metastases, and achieved longer disease control effect.
• Patients voluntarily participated in this study and signed informed consent;
• Patients ≥18 years old;
• ECOG score ≤2 points; Expected survival ≥6 months;
• Pathological diagnosis of adrenal cortical carcinoma;
• Inability or unwillingness to surgically resect recurrent or metastatic adrenal cortical cancer;
• Adrenal cortical cancer has recurred or metastasized after receiving mitotan monotherapy, chemotherapy, or first-line regimens based on mitotan combined with cisplatin chemotherapy and has progressed, unable to tolerate or unwilling to accept the regimens;
• Have at least one measurable lesion (RECIST1.1);
• The main organs function well, and the laboratory examination indicators meet:
• (1) Blood routine examination: Hemoglobin (HB) ≥90g/L(5.6mmol/L); Absolute neutrophil count (ANC) ≥1.5×109/L; Total white blood cells ≥3.5×109/L;
‣ Platelet (PLT) ≥80×109/L; (2) Blood biochemical examination:
‣ ① Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (liver metastasis/bone metastasis ≤5× ULN; Tumor bone metastasis ≤5ULN);
‣ ② Serum total bilirubin (TBIL) ≤1.5×ULN;
⁃ Serum creatinine Cr≤1.5×ULN or creatinine clearance ≥60ml/min; Blood urea nitrogen (BUN)≤2.5× upper limit of normal value (ULN); ④ Albumin (ALB)≥30g/L; (3) Blood coagulation test: Activated partial thromboplastin time (APTT), International Normalized ratio (INR), prothrombin time (PT) ≤1.5×ULN;
• Women of childbearing age must confirm their non-pregnant status before enrollment, and all enrolled subjects (whether male or female) should take adequate contraceptive measures during the whole treatment period and 4 weeks after the end of treatment;
• The subjects were willing to return to the hospital for follow-up and had good compliance.