Prof. Thomas Powles (Barts Cancer Institute, UK) presented the results of phase 3, multicentre, multinational, randomized, open-label, parallel-arm JAVELIN Bladder 100 study in patients with locally advanced or metastatic urothelial cancer whose disease did not progress after completion of first-line, platinum-containing chemotherapy. The study met its primary endpoint by showing significantly longer overall survival with avelumab first-line maintenance versus control, both in the overall population and the PD-L1+ population .
First-line, platinum-based chemotherapy for advanced bladder cancer is characterized by frequent resistance, and PD-L1/PD-1 inhibitors, such as avelumab, are a standard second-line treatment for patients with disease progression; however, only a minority of patients obtain a durable clinical benefit . The JAVELIN Bladder 100 trial investigated avelumab as first-line maintenance therapy in patients whose disease had not progressed with first-line platinum-based induction chemotherapy.
Participants (n=700) underwent 4-6 cycles of standard platinum-based chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine), followed by a treatment-free interval between 4-10 weeks. Then, 350 patients were randomized to receive avelumab (10 mg/kg IV Q2W) and best supportive care (BSC) (e.g. antibiotics, nutrition, hydration, pain management), while the other 350 patients received BSC alone. Co-primary endpoints were overall survival in (1) all randomized patients, and (2) the PD-L1+ population. Secondary endpoints were progression-free survival, objective response per RESIST 1.1, safety and tolerability, and patient-reported outcomes.
The primary endpoints were both met; the median overall survival for the avelumab + BSC arm was 21.4 months versus 14.3 months for BSC alone in the overall population (HR 0.69; 95% CI 0.56-0.86; P<0.001), and was better in the PD-L1+ patients as well; (n=61/189 in the avelumab + BSC arm; n=82/169 in the BSC alone arm; HR 0.56; 95% CI 0.40-0.78). However, Prof. Powles pointed out that the patients that had PD-L1- negative or unknown status also showed benefit, and that all prespecified subgroup analyses broadly favored the avelumab group.
The secondary progression-free survival endpoint was also significant; in the avelumab + BSC arm, progression-free survival was 3.7 months as compared with 2.0 months for BSC alone (HR 0.62; 95% CI 0.52-0.75; P<0.001). The safety profile of avelumab as first-line maintenance was manageable and consistent with previous studies of avelumab monotherapy.
In conclusion, this late-breaker abstract highlights the statistically significant improvement in overall survival observed with the combination of the PD-L1 inhibitor avelumab + best supportive care, versus best supportive care alone in patients with advanced urothelial carcinoma that followed platinum-based chemotherapy in the frontline setting. Based on the JAVELIN Bladder 100 findings, the FDA has granted a breakthrough therapy designation to avelumab in this setting. Prof. Powles closed his presentation by stating that “overall, avelumab first-line maintenance in patients whose disease has not progressed with platinum-based induction therapy is a new first-line standard of care of advanced urothelial cancer.”
1. Powles T. Phase III interim analysis examining maintenance treatment with the immunotherapy avelumab after platinum-based first-line chemotherapy in advanced bladder cancer. ASCO Virtual Meeting, 29-31 May 2020, Abstract LBA1.
2. Simeone JC, et al. Treatment patterns and overall survival in metastatic urothelial carcinoma in a real-world, US setting. Cancer Epidemiol. 2019;60:121‐127.