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Avelumab frontline maintenance benefit sustained across subgroups in bladder cancer


An analysis from the pivotal phase 3 JAVELIN Bladder 100 trial showed that the survival benefit observed with frontline maintenance avelumab in the overall population was sustained across several prespecified patients subgroups.

The latest findings from the pivotal phase 3 JAVELIN Bladder 100 trial showed that frontline maintenance with avelumab (Bavencio) extended overall survival (OS) and progression-free survival (PFS) across several key subgroups of patients with advanced or metastatic urothelial carcinoma that had not progressed on upfront platinum-based chemotherapy.1

The subgroup analysis, which was presented during the 2020 ESMO Virtual Congress, showed a significant OS and PFS improvement with avelumab, irrespective of the degree of response to frontline chemotherapy or the specific induction chemotherapy regimen administered.

“The JAVELIN Bladder 100 saw that avelumab significantly prolonged OS and PFS, and this benefit was regardless of which induction chemotherapy the patient received, or the best response to that chemotherapy,” lead study author Petros Grivas, MD, PhD, associate professor in the Division of Medical Oncology of University of Washington School of Medicine; clinical director of the Genitourinary Cancers Program; and associate professor in the Clinical Research Division at Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, said in a virtual presentation during the meeting.

Previously reported findings from the JAVELIN Bladder 100 study formed the basis of the June 2020 FDA approval of avelumab as a maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-based chemotherapy.2 Here, data showed a 7.1-month improvement in median OS with avelumab as frontline maintenance treatment plus BSC versus BSC alone.3

In the overall patient population, the median OS was 21.4 months with the addition of avelumab versus 14.3 months with best supportive care (BSC) alone, which translated to a 31% reduction in the risk of death in the overall patient population (HR, 0.69; 2-sided P = .001).

“Based on these data, the FDA approved avelumab as switch maintenance therapy in the frontline setting […] and subsequently the NCCN and ESMO guidelines changed, showing that this study was completely practice changing,” Grivas said.

The multicenter, international, open-label phase 3 JAVELIN Bladder 100 trial randomized patients to frontline avelumab maintenance therapy in combination with BSC (n = 350) or BSC alone (n = 350). Enrolled patients had unresectable locally advanced or metastatic urothelial cancer that did not progress on 4 to 6 cycles of standard gemcitabine paired with either cisplatin or carboplatin.

Treatment was given between 4 to 10 weeks post induction chemotherapy. Fifty-one percent of patients had PD-L1–positive tumors. BSC included antibiotics, nutritional support, correction of metabolic disorders, as well as symptom control and pain management, and the chemotherapy regimen administered was either gemcitabine/cisplatin (n = 389) or gemcitabine/carboplatin (n = 269).

The baseline characteristics in patient subgroups reflected physician’s choice of first-line chemotherapy regimen. The median age in the gemcitabine/cisplatin–treated group was 66.5 years compared with 72.5 years in the gemcitabine/carboplatin–treated cohort. More patients on gemcitabine/cisplatin had an ECOG performance status of 0 (median, 67%) versus those on gemcitabine/carboplatin (median, 52%).

More patients on gemcitabine/cisplatin (64%) had 60 or higher mL/min creatinine clearance versus those who received gemcitabine/carboplatin (40%). More than half of patients in both chemotherapy groups had visceral metastasis (57.5% vs 51%, respectively), and roughly as well as those who had PD-L1–positive status (51% vs 47%). The best response to chemotherapy was 72% for patients on gemcitabine/cisplatin versus 70% for those on gemcitabine/carboplatin.

Median follow-up periods were 19.6 months in the avelumab arm and 19.2 months in the BSC-alone arm. In the overall patient population, the median PFS was 3.7 months in the avelumab-plus-BSC arm compared with 3.7 months in the BSC-alone arm per blinded independent central review (HR, 0.62; P <.001). Additionally, the HR for PFS favored avelumab in the PD-L1–positive subgroup, as well (HR, 0.56).

The results also demonstrated that in the cohort of patients with PD-L1–positive tumors, the median OS had not yet been reached in those who received avelumab versus 17.1 months in those who received BSC alone (HR, 0.56; P = .0003).

When stratified by chemotherapy regimen, the OS and PFS benefit with avelumab as frontline maintenance was demonstrated irrespective of the induction chemotherapy regimen. With gemcitabine/cisplatin plus avelumab, the median PFS was 4.6 months versus 2.0 months for chemotherapy alone (HR, 0.63). The median OS was 25.3 months with avelumab versus 16.5 months without (HR, 0.69)

Among patients who received frontline chemotherapy with gemcitabine/carboplatin plus avelumab, the median PFS was 3.0 months versus 1.9 months for chemotherapy alone (HR, 0.59). The median OS was 19.9 months and 12.9 months, respectively (HR, 0.66).

“The different baseline characteristics were relatively well balanced between best supportive care and the avelumab arm, and this was the case in the subset of patients with complete response, partial response, or stable disease to prior induction chemotherapy,” Grivas said.

The survival benefits with frontline maintenance avelumab plus BSC were observed irrespective of best response to induction chemotherapy (complete response, partial response, or stable disease).

Further, the OS benefit with the addition of avelumab as frontline maintenance therapy in this setting was observed across additional subgroups, regardless of whether patients were younger than 65 years (HR, 0.79) or older (HR, 0.63), had an ECOG performance status of 0 (HR, 0.64) or 1 (HR, 0.74), a creatinine clearance of lower or higher than 60 mL/min (HR, 0.68), and whether patients were PD-L1 positive (HR, 0.56), negative (HR, 0.86), or unknown (HR, 0.69). Regarding the site of baseline metastasis, the HR for patients with visceral metastasis was 0.82 and was 0.54 for those with nonvisceral metastasis; HRs were 0.86 and 0.63 in those with and without lung lesions at baseline, respectively.

Additional subgroup data showed that the addition of avelumab to BSC was reported whether patients were male (HR, 0.64) or female (HR, 0.89); White (HR, 0.67), Asian (HR, 0.70), or other (HR, 0.91); from Europe (HR, 0.64), North America (HR, 0.86), Asia (HR, 0.71), and rest of world (HR, 0.38). The most modest benefit was seen in patients from Australia (HR, 0.96).


1. Grivas P, Park SH, Voog E, et al. Avelumab 1L maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy for advanced urothelial carcinoma: subgroup analyses from JAVELIN Bladder 100. Presented at: 2020 Virtual ESMO Congress; September 19-21, 2020; virtual. Abstract 704MO.

2. FDA approves Bavencio as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. News release. Pfizer. June 30, 2020. Accessed June 30, 2020. bit.ly/2YO7gVk.

3. Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. J Clin Oncol. 2020;38(suppl 18):LBA1. doi:10.1200/JCO.2020.38.18_suppl. LBA1.

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