Discussion
cancer, tumor, death, physician-choice
CANCER, TUMOR
To improve the outcome of rGBM, it is critical to use chemotherapies that are effective against the CSCs as they are proven to drive tumor development and relapse. We conducted a randomized clinical trial using the ChemoID CSC assay to guide chemotherapy for rGBM treatment. It is worth noting that patients in both arms were treated with a regimen chosen from the same panel of chemotherapy medications, with one group using the patient-specific ChemoID test report to guide chemotherapy selection and the other relying on the physicians’ best judgment.Planned interim efficacy analysis showed that the ChemoID-guided group’s mOS was 3.5 months longer than the physician-choice group’s (12.5 vs. 9 months) (In the ITT analysis, the study continued to meet its primary endpoint. The mOS was 4.5 months longer for the ChemoID-guided group compared with the physician-choice group (12 vs. 7.5 months) (To confirm the validity of the data analysis using the HR method to summarize the difference in survival curves between the two arms as described in the approved study protocol, we also analyzed the data using RMST. By analyzing the 1- or 1.5-year RMST and CIs for each of our primary results, we found that subjects who received ChemoID-guided therapy had a significant survival advantage, which proves that using other robust statistical analysis methods, the survival differences between the two groups were statistically significant. The data support the use of the ChemoID assay for guiding chemotherapy selection for rGBM. The OS and PFS advantages observed for the ChemoID-guided group are not due to differences in prognostic variables, such as age, sex, performance status, The current SOC treatment protocol for GBM is a combination of surgical resection, radiotherapy, and concomitant TMZ chemotherapy followed by maintenance TMZ as demonstrated in the EORTC-NCIC trial.Of note, the use of anti-CSC-guided therapy resulted in a 3.5-month mOS advantage when compared with the control group in the population evaluated at the interim efficacy analysis and a 4.5-month mOS advantage in the ITT population. A significant difference was observed in the risk of death between the two groups. More participants survived in the ChemoID assay-guided group compared with the non-guided group at 6, 9, and 12 months, demonstrating that patients with rGBM derive a survival benefit from treatment with CSC-directed therapy.In conclusion, the ChemoID assay was developed as an actionable tool for physicians to individualize cancer treatment by selecting the most effective therapies against CSCs from a panel of cytotoxic agents that are common and affordable for cancer patients. Treatments with more expensive targeted anti-cancer drugs and immunotherapies are not always feasible due to socioeconomic and health disparity issues in the US and around the world. Although there are newer targeted therapies, our clinical trial focused on screening SOC chemotherapies that are routinely covered and used by community oncologists globally. The results of our study highlight the clinical effectiveness of a personalized approach to treatment. The ability of the ChemoID assay to personalize chemotherapy selection is a promising way to provide more affordable treatment for patients with rGBM. The ChemoID assay is versatile, allowing it to be expanded to include other new agents. We anticipate personalized anti-cancer therapy targeting CSCs will be included sooner in the treatment plan, eliminating ineffective treatments and allowing patients to gain the greatest therapeutic benefit possible.