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Upfront immunotherapy regimen falls short in bladder cancer


The addition of avelumab to standard first-line gemcitabine/carboplatin did not improve outcomes in patients with metastatic urothelial carcinoma.

Induction immunotherapy followed by chemoimmunotherapy did not significantly improve outcomes versus chemotherapy alone in the frontline setting for patients with metastatic urothelial carcinoma (mUC), according to findings presented at the 2020 ESMO Congress.1

In a phase 2 study, treatment-naïve patients who were ineligible for cisplatin-based chemotherapy were randomized to 2 cycles of induction avelumab (Bavencio) followed by 6 cycles of avelumab plus gemcitabine/carboplatin followed by avelumab maintenance therapy (n = 42) or standard of care (SOC) gemcitabine/carboplatin alone (n = 43). The overall response rates were 57.1% (24/42) in the avelumab arm and 53.5% (23/43) in SOC arm (P = .73). Specifically, 45.2% and 11.9% of patients in the avelumab arm experienced partial and complete responses, respectively, compared with 44.2% and 9.3% in the SOC arm.1,2

The median PFS was 6.9 months in the avelumab arm versus 7.4 months in the SOC arm (P = .1356). Further, the median OS benefit was 10.5 months versus 13.2 months (P = .2642), respectively.1,2

“The main objective of obtaining a 45% response rate was achieved in the avelumab treatment arm, however a similar response rate was unexpectantly observed in the chemotherapy treatment arm,” Begoña P. Valderrama, MD, of the Hospital Universitario Virgen del Rocío, in Sevilla, Spain, said during a presentation of the data at ESMO. “Induction immunotherapy alone before chemotherapy and immunotherapy is not an adequate strategy. The previous hypothesis that immunotherapy before chemotherapy might optimize chemotherapy response was not proven.”

Higher rates of disease progression and death were observed in the avelumab arm. Thirteen patients (31%) progressed or died prior to the first response assessment, and 6 of the deaths occurred in the first month. Only 4 patients progressed or died in the SOC arm.1 No adverse prognostic factor imbalance was observed in these patients, Valderrama explained.

In terms of safety, treatment related adverse-events (AEs) grade 3 or higher were reported in 70.7% and 65.1% of patients, respectively. In the avelumab arm, 41.5% grade 3 AEs were associated with avelumab. “No new unexpected toxicities were found beyond the ones that were already know with each of the agents given alone,” Valderrama said.

In a planned post-hoc analysis censoring all patients who died in the first 30 days (n = 6), the PFS data demonstrated similar results in both arms: 7.4 months in both the avelumab and placebo arms P = .7755). Further, at 15 months follow-up a superior percentual benefit in OS was observed in patients who received avelumab plus chemotherapy followed by avelumab maintenance. OS survival rates for avelumab versus placebo were 51.25% (95% CI, 33.64%-66.41%) and 38.96% (95% CI, 21.84%-55.76%), respectively.1 The follow-up data are still immature, but are consistent with the findings seen in the Javelin Bladder 100 maintenance study (NCT02603432), Valderrama said.

Avelumab retains its position as the preferred regimen for patients who are cisplatin ineligible as maintenance therapy following gemcitabine and carboplatin. On June 30, 2020, the FDA approved the agent as maintenance treatment for patients with locally advanced or mUC that has not progressed with first-line platinum-based chemotherapy. The approval added to the 2017 indication in mUC for patients who have disease progression during or following platinum-containing chemotherapy, or experience disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.3


  1. Valderrama BP. Phase II multicenter, randomized study to evaluate efficacy and safety of avelumab with gemcitabine/carboplatin (CG) vs CG alone in patients with unresectable or metastatic urothelial carcinoma (mUC) who are ineligible to receive cisplatin-based therapy. Abstract presented at: 2020 European Society for Clinical Oncology Virtual Congress.; September 18-21, 2020; virtual. LBA27. https://cslide.ctimeetingtech.com/esmo2020/attendee/confcal_1/session
  2. Gust KM. What’s the future of IO in urothelial carcinoma? How to combine or sequence the old and the new? Discussion presented at: 2020 European Society for Clinical Oncology Virtual Congress.; September 18-21, 2020; virtual. Presentation ID 5007. https://cslide.ctimeetingtech.com/esmo2020/attendee/confcal_1/session
  3. FDA approves avelumab for urothelial carcinoma maintenance treatment. News release. FDA. Updated July 1, 2020. Accessed September 18, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment
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