Pfizer and Merck Announce Bavencio Significantly Extends Overall Survival by Over 7 Months in First-Line Maintenance Treatment of Advanced Urothelial Carcinoma

Compiled by Keke

At the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, Pfizer and Merck KGaA will present the positive interim analysis results from the Phase 3 JAVELIN Bladder 100 clinical trial, which evaluated maintenance therapy with the anti-PD-L1 agent Bavencio (avelumab) plus best supportive care (BSC) versus BSC alone in patients with advanced urothelial carcinoma (UC) following platinum-based chemotherapy.

Platinum-based chemotherapy is an effective first-line treatment regimen for patients with advanced urothelial carcinoma (UC); however, due to the development of resistance, progression-free survival (PFS) and overall survival (OS) are typically short. The JAVELIN Bladder 100 study evaluated the efficacy of avelumab as maintenance therapy in patients with advanced UC who had achieved a response or stable disease following first-line platinum-based chemotherapy.

This trial enrolled 700 patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) who had no disease progression after 4–6 cycles of gemcitabine combined with cisplatin or carboplatin. Patients were randomized in a 1:1 ratio to receive either avelumab maintenance therapy (10 mg/kg intravenously every 2 weeks) plus best supportive care (BSC) or BSC alone. Stratification was performed based on the best response to first-line chemotherapy (complete/partial response versus stable disease) and the presence of visceral versus non-visceral disease at the initiation of first-line chemotherapy. The primary endpoint was overall survival (OS), assessed in two predefined populations: all randomized patients and PD-L1–positive patients (as determined by the Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS), objective response rate, and drug safety.

The median follow-up times for patients in the avelumab + BSC and BSC-only treatment groups were 19.6 months and 19.2 months, respectively. Among all enrolled patients, 358 tested positive for the tumor biomarker PD-L1. The results showed that, compared with BSC alone, avelumab + BSC significantly prolonged overall survival (OS) in patients (hazard ratio [HR] 0.69; 95% CI 0.56, 0.86; one-sided p=0.0005);The median OS for the avelumab + BSC group and the BSC-alone group was 21.4 months and 14.3 months, respectively, representing an extension of over 7 months in patient OS.。

In PD-L1+ patients, avelumab + BSC significantly prolonged OS (HR 0.56; 95% CI 0.40, 0.79; 1-sided p=0.0003), with median OS not yet reached, compared to 17.1 months in the BSC-alone group. OS benefits were also observed in all prespecified subgroups.

Based on blinded independent central review, the hazard ratio for PFS was 0.62 (95% CI 0.52, 0.75) for avelumab + BSC versus BSC alone in all randomized patients; in PD-L1+ patients, the hazard ratio was 0.56 (95% CI 0.43, 0.73). JAVELIN Bladder 100 met its primary endpoint, demonstrating that first-line maintenance therapy with avelumab + BSC significantly prolonged OS compared with BSC alone in patients with advanced UC, both in the overall randomized population and in the PD-L1+ subgroup. Efficacy benefits were observed across all prespecified subgroups.

Meanwhile, the incidence rates of all-cause adverse events (AEs) of any grade in the avelumab + BSC group and the BSC-alone group were 98.0% and 77.7%, respectively; the incidence rates of AEs ≥ Grade 3 were 47.4% and 25.2%, respectively. The most common ≥ Grade 3 AEs were urinary tract infection, anemia, hematuria, fatigue, and back pain. The safety results were consistent with those from previous monotherapy studies.

Avelumab is a PD-L1 antibody that has demonstrated adaptive and innate immune functions in preclinical models. In November 2014, Merck KGaA and Pfizer announced the joint development and commercialization of this drug. Currently, avelumab is approved in the United States for the first-line treatment of patients with advanced renal cell carcinoma (RCC) in combination with axitinib; as monotherapy for adults and pediatric patients aged 12 years and older with metastatic Merkel cell carcinoma (MCC); and as monotherapy for locally advanced or metastatic urothelial carcinoma (UC) in patients who have experienced disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

For Bavencio, these study results represent a major victory, marking the first time an immuno-oncology drug has competed in the first-line maintenance setting. The market competition for PD-1/PD-L1 inhibitors in the later-stage treatment of bladder cancer has become intensely fierce. Beyond urothelial carcinoma (UC), other approved indication areas for Bavencio are also crowded: Keytruda dominates the Merkel cell carcinoma (MCC) market, while both Keytruda and Opdivo compete in the renal cell carcinoma (RCC) market. If these trial data lead to FDA approval for Bavencio, Pfizer and Merck KGaA will be the only companies with a PD-L1 inhibitor approved for first-line maintenance therapy.

Reference Source: ASCO20: Merck KGaA, Pfizer's Bavencio Prolongs OS by 7.1 Months in Bladder Cancer Trial