ASCO 2020: Maintenance Therapy with Avelumab Post-Chemo Improves Overall Survival of Bladder Cancer Patients
By Ruchi Jhonsa, Ph.D.
Bladder cancer is the 6th most common cancer in the US and is responsible for 200,000 deaths globally in 2018. The current standard of care for this disease is platinum-based chemotherapy. Although the majority of patients respond, the progression-free survival and overall survival are short due to resistance posed by the cancer cells against the treatment. The standard second line of therapy for these patients is treatment with avelumab (Bavencio), a human anti-PD-L1 antibody co-developed by Merck KGaA and Pfizer. The drug has been shown to engage both the adaptive and innate immune functions in preclinical models. However, just 25-55% of patients receive this second line of treatment, and only a minority benefit from it.
Avelumab (Bavencio) as First-Line Maintenance Therapy
The Phase 3 JAVELIN bladder 100 trial investigated avelumab as the first-line maintenance therapy in patients whose disease had not progressed with first-line platinum-based induction therapy. The interim results from this trial were presented at the virtual ASCO meeting. The analysis showed that avelumab plus best supportive care (BSC) “significantly extended” the survival of patients making it the “first immunotherapy to demonstrate a statistically significant improvement in overall survival in Phase 3 clinical trial for patients with locally advanced or metastatic urothelial carcinoma.” Based on these encouraging results, Bavencio was granted breakthrough designation by the USFDA last month to accelerate the development and review of the drug for urothelial carcinoma treatment.
“Given the poor prognosis for patients with advanced urothelial carcinoma, there is an urgent need for additional treatment options that improve overall survival,” said Luciano Rossetti, Head of Global R&D for the Biopharma business of Merck KGaA, Darmstadt, Germany. “Our data highlight the potential for a first-line maintenance treatment approach with BAVENCIO to advance the current standard of care for previously untreated patients, and we are working with urgency toward our goal of bringing this regimen to patients.”
JAVELIN Bladder 100 Trial
This Phase 3 study enrolled a total of 700 patients whose disease was stable after the first-line treatment with platinum-based therapy. These patients were randomized to receive avelumab plus BSC or BSC alone. The study assessed the improvement in overall survival and progression-free survival as well as tolerance and drug safety in each of the co-primary populations of all randomized patients and patients with PD-L1 positive tumors. The overall survival of patients on avelumab immunotherapy (21.4 months) was seven months higher than that of patients who were on BSC alone (14.3 months).
Upon admission, patients were divided into different subgroups depending upon:
- The chemotherapy regimes they were on or
- Their response to chemotherapy and
- The site of baseline metastasis.
Interestingly, the analysis of the overall survival showed that the treatment worked across broad groups and subgroups of patients. Moreover, the hazard ratio (which determines the occurrence of an adverse event) in the treatment group vs. the control group was mostly under 0.8 for all the subtypes, which is an indication of functional treatment. Additionally, the PD-L1 positive patients showed a hazard ratio of 0.56 versus the PD-L1 negative patients’ 0.86. This strongly indicates that avelumab therapy is working via its inhibitory effects on PD-L1 ligand on the cancer cells.
Although not drastic, progression-free survival was also improved in patients on avelumab maintenance therapy (3.7 months) as compared to BSC alone (2.0 months). Together, these two survival data support the superiority of avelumab maintenance therapy over chemotherapy alone. Additionally, the drug was found to be well-tolerated, and its safety profile was found comparable to that of the JAVELIN monotherapy clinical development program.
“For the past 30 years, chemotherapy has been the first-line standard of care for patients with advanced urothelial carcinoma. While this is an effective short-term option for many patients, most will ultimately experience disease progression, underscoring a need for additional treatment options,” said Petros Grivas, M.D., Ph.D., one of the principal investigators in the JAVELIN Bladder 100 trial. “Based on the positive overall survival results from JAVELIN Bladder 100, I believe avelumab has the potential to be practice-changing.”
Editor: Rajaneesh K. Gopinath, Ph.D.
- J Clin Oncol 38: 2020 (suppl; Abstr LBA1)
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