Baseline Circulating Tumor DNA Association with Immunotherapy Drugs

Release Date: 03-Aug-2020

Immunotherapy has been an overwhelming therapy available for the cancer patients as its arrival in the cancer markets has increased the overall survival rate of the cancer patients. Identification of baseline circulating tumor DNA levels are now associated with the prognosis of the treatment with pembrolizumab for the patients who have been suffering from different types of cancer. Baseline circulating tumor DNA is considered to be important for the prognostication and the response monitoring according to the research conducted.                        

The above mentioned prospective was studied in a trial that included 94 patients. The different types of cancer patients who were enrolled in the trial were malignant melanoma, high-grade serous ovarian cancer, head and neck squamous cell carcinoma and mixed solid tumors (MST). All the patients enrolled in the study were treated with pembrolizumab.  For the analysis of the baseline circulating tumor DNA assay, the sequencing method that was used was whole-exome sequencing. It helped in developing assay for each and every patient enrolled in the patient. Through the sequencing it was identified that were 16 somatic mutations present. It reflected that variant allele frequency for all tested variants was calculated to improve baseline circulating tumor DNA detection.

According to the analysis that was performed ctDNA was detected to be ranging from 0.004% to 0.07 mean tumor molecules per mL of plasma. It was concluded from this that the tumor target size was not at all associated with the levels of baseline ctDNA. But the progression free survival was found to be linked with the lower baseline ctDNA levels. Also higher clinical benefit rate in the patients was found to be linked with the baseline levels of ctDNA below the median.

At last, it was concluded that an increase in the baseline level of ctDNA was linked with poor survival and rapid disease progression. The amount of ctDNA level that was detectable was linked with mixed response in the patient. During the course of the treatment, superior clinical outcomes were observed when ctDNA was cleared. This was observed in 12 patients in which 100% overall survival rate was observed. Also, it was found during the course of the study that baseline ctDNA and change in ctDNA was weekly associated with PD-L1 experssion. But there was no association found with the tumor mutational burden or high levels of microsatellite instability. It was suggested that the study was important and had broad range of aapplications for the cancer patients in immune checkpoint blockade-treated patients.