In my opinion, the two predominant themes at the 50th annual ASCO meeting this year were genomics and immune therapies. Both of these fronts have seen major advances in recent years, and both fields were very strongly represented by investigators from around the world.
One of the things I found most exciting to watch was the series of presentations focusing on unleashing the potentials of the immune system in genitourinary cancers-an area with a great need for effective, novel therapeutic approaches.
Ground-breaking results were presented by Dr. Thomas Powles, Senior Lecturer in Urology Cancer and Honorary Consultant in Medical Oncology at Barts and the London Medical School. He discussed his abstract on the Phase I study of inhibition of PD-L1 by MPDL3280A in patients with metastatic bladder cancer. As the response rate data was displayed, one could almost hear a collective sigh of relief at the overcrowded Aerie Crown Theater, one of the biggest presentation halls at the McCormick Place.
These 68 patients had advanced disease that had progressed through two or more prior lines of chemotherapy, with 75% having visceral metastasis. In such a setting, any single-agent cytotoxic approach is expected to provide a response rate on the order of 5-10%, with a dismal prognosis. There are no approved agents for second- or third-line treatment of metastatic urothelial cancer.
The authors were proud to present a tantalizing overall response rate of 52%, with two patients achieving a complete radiological response. Patients who responded included those with visceral metastasis, and all of them continued to show a response at the time of clinical cutoff. Making this approach even more promising, the exceptional safety profile of the drug was unmatchable (as least in this early phase clinical trial). The investigators utilized 15mg/kg of MPDL3280A intravenously every three weeks for up to one year. There were only 4% grade 3-4 toxicities, with no immune-related adverse events or any nephrotoxicity. As correlative analyses, this early phase trial also looked into early development of predictive biomarkers, including PD-L1 expression on tumor cells. Also, some encouraging preliminary results of circulating pharmacodynamic markers were presented; thus adding to the body of scientific knowledge to further this type of treatment course.
One can easily label such a safety and efficacy profile as ‘too good to be true’, considering experience from other agents in the broad class of immune therapies and the overall health status of this patient population. Nonetheless, the oncology community will be eagerly waiting for definitive trials (e.g NCT 02108652) and eager to make improvements in clinical practice. At the very least, this is a major advance in a tough disease and it has the potential to provide another pillar of treatment for these cancers.
This anti-PD-L1 agent, MPDL3280A, has rightfully been given Breakthrough Therapy Designation by the Food and Drug Administration-the first of its kind in bladder cancer.