The checkpoint inhibitor revolution began in February of last year with the approval of the PD-1 inhibitor nivolumab for the treatment of locally advanced or metastatic bladder cancer following disease progression on or after traditional platinum-based chemotherapy. Results from the phase II CheckMate 275 trial showed 19.6% of patients demonstrated a response on nivolumab.
By the end of May, nivolumab was no longer alone— every other late-stage PD-1 or PD-L1 inhibitor under investigation was approved for urothelial cancer in rapid succession. First, durvalumab, a PD-L1 inhibitor was approved under the same indication as nivolumab after a phase I/II trial demonstrated an overall response rate (ORR) of 17.8%. Next was avelumab, another PD-L1 inhibitor with the same indication. Results from the phase I JAVELIN Solid Tumor trial demonstrated an ORR of 16.1% at the time of approval. Subsequent publications have shown a slightly increased ORR.
A week after the approval of avelumab, pembrolizumab was approved, also for the treatment of locally advanced or metastatic bladder cancer. Support for pembrolizumab’s approval came from the phase III KEYNOTE-045 trial, the results of which demonstrated an ORR of 21.1% for patients on the PD-1 inhibitor. Across all patient populations, including high expressers of PD-L1, median OS increased by nearly 3 months. Pembrolizumab was approved on the same day, one year later, as atezolizumab, a PD-L1 inhibitor, with the same indication.
In a further groundbreaking advancement for checkpoint inhibition, also in May, the FDA issued the first tissue-agnostic approval for pembrolizumab for patients with unresectable or metastatic, microsatellite instability-high, or mismatch repair deficient, solid tumors that have progressed following initial treatment.
Rounding out a year of advancement in genitourinary malignancies, September saw the approval of lower dose cabazitaxel, a microtubule inhibitor, in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer. November brought us the approval of sunitinib, a small molecule receptor tyrosine kinase, for the adjuvant treatment of patients at high risk of recurrence of renal cell carcinoma (RCC) following surgical resection. Then, finishing the year cabozantinib was approved for advanced RCC in late December.