A previous trial showed that Yervoy did not extend survival when used in men who were metastatic and castration-resistant (mCRPC) and who had failed chemotherapy. This is often the first group given a new drug because other options have been exhausted and because it takes less time to prove efficacy. Researchers hoped that it might have some effect if used earlier in disease progression. Unfortunately, it did not.
Beer et al. tested Yervoy this time in men who were metastatic and castration-resistant but who had not yet tried chemotherapy and who were asymptomatic or minimally symptomatic (i.e., no bone pain or organ dysfunction). In this multi-institutional study, there were 399 patients who got Yervoy, and 199 who got a placebo. Neither patients nor doctors knew who got which.
- Patients were given 10 mg/kg of Yervoy or placebo every 3 weeks for up to 4 doses.
- Therapy was repeated every 3 months thereafter to non-progressing patients
- Median overall survival was 28.7 months for those who got Yervoy vs. 29.7 months for those who got the placebo (no statistically significant difference).
- Median progression-free survival was 5.6 months or those who got Yervoy vs. 3.8 months for those who got the placebo (a statistically significant difference).
- 23% had a PSA response with Yervoy vs. 8% with the placebo.
- Death that was treatment-related in 9 patients (2%).
- Serious or life-threatening immune-related adverse events in 31%
- Serious or life-threatening diarrhea in 15%
Research continues on other checkpoint blockers. Keytruda has been approved for melanoma, lung cancer and head-and-neck cancer. In addition to Keytruda, there are several investigational immunotherapies targeting the PD-1/PD-L1 antigen. It may turn out that checkpoint blockers work better in combination with other immunotherapies (like Provenge or ProstVac), or perhaps they need to be primed with concurrent SBRT radiotherapy or chemotherapy. We need a better understanding about why an immunotherapy may work very well for one cancer, but very poorly for another cancer, We also can't lose sight of the fact that all immunotherapies may be lethal. There is clearly much to be learned.