Medivation/Astellas Pharma's MDV3100 took center-stage at the annual ASCO Genitourinary Cancers Symposium, and was heralded as practice-changing treatment for metastatic castration-resistant prostate cancer (mCRPC). MDV3100 becomes the fifth novel agent to significantly improve median overall survival (MOS) in mCRPC in less than three years.
Data from the Phase III AFFRIM trial showed that MDV3100 extended MOS by almost 5 months over placebo (18.4 months versus 13.6 months, respectively; P < 0.0001) in mCRPC patients who had received prior chemotherapy. Eagerly anticipated data of secondary efficacy end points were also met. Most notably, treatment with MDV3100 extended median radiographic progression-free survival (rPFS) compared with placebo (8.3 months versus 2.9 months, respectively; P < 0.0001) and improved PSA response rates (defined as at least a 50% decline in PSA levels from baseline) (54% versus 1.5%; respectively; P < 0.0001). MDV3100 also has an enviable safety and tolerability profile, as evidenced by data showing that MDV3100 displayed fewer adverse events than placebo. Concerns over the frequency of seizures observed in earlier studies were quashed; the grade 3 or higher frequency of seizure in the MDV3100-treatment group (0.6%) is likely too small to establish a causal relationship.
Over the last 2-3 years there has been a surge in new diverse treatments for prostate cancer Dendreon's Provenge (sipuleucel-T), Sanofi's Jevtana (cabazitaxel), GlaxoSmithKline/Daiichi Sankyo/AstraZeneca's Xgeva (denosumab), Johnson & Johnson/Janssen Biotech/Janssen-Cilag's Zytiga (abiraterone) ending decades of stagnation. To further add to this list of agents, Algeta/Bayer Healthcare's radium-223 (Alpharadin), an alpha-emitting radiopharmaceutical, has also demonstrated a statistically significant improvement in MOS in progressive, symptomatic mCRPC patients who are ineligible to receive docetaxel. Filing for regulatory approval of Alpharadin is anticipated in mid-2012. MDV3100 will increase treatment options for mCRPC patients in the post-docetaxel setting even further and will surely pose a serious threat to Zytiga, which was granted FDA approval in April 2011.
The growing number treatments for mCRPC underscore the dynamism of the prostate cancer market. The prostate cancer landscape is now entering a new era of intense competition where we will see varied treatment strategies vie for patient share and pole position. It will become increasingly important for developers to differentiate their agents over those currently available. With new agents such as MDV3100 and Alpharadin showing impressive MOS advantage the gold standard end point for obtaining regulatory approval and a rich pipeline of therapies waiting in the wings, we forecast that the prostate cancer market will soar to in excess of $10 billion by 2020.
However, the emergence of a plethora of treatments for mCRPC and resultant increased complexity of medical practice has unveiled an air of uncertainty over the optimal choice of treatment in any given mCRPC setting. Arguably, this is a nice problem to have after a long period of drought in effective treatments options. There is now unquestionably a pressing need to understand the most effective sequence of treatments. Many questions remain unanswered: Should novel agents be used in combination with one another? If so, which combinations? Or should treatments be prescribed sequentially? Further clinical trials can only unequivocally answer these important questions. Identification of markers that predict which patients will most likely benefit from each treatment will also be pivotal for assisting effective and efficient decision-making in mCRPC.