Frontline Avelumab Maintenance Provides Prolonged Survival Benefit in Urothelial Carcinoma

The addition of avelumab (Bavencio) maintenance therapy to best supportive care (BSC) prolonged survival in patients with metastatic urothelial cancer regardless of the response achieved with first-line chemotherapy, solidifying this regimen as a standard-of-care (SOC) option in the first-line setting, according to Shilpa Gupta, MD.¹

In June 2020, the FDA approved avelumab maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed on first-line platinum-based chemotherapy. This decision was based on prior results from the phase 3 JAVELIN Bladder 100 trial (NCT02603432), in which the addition of avelumab maintenance therapy to best supportive care (BSC) significantly improved median overall survival (OS) vs BSC alone (HR, 0.69; 95% CI, 0.56-0.86; P = .001).²

Results from an exploratory subgroup analysis of the trial were presented at the 2023 American Urological Association (AUA) Annual Meeting.¹ At a median follow-up of at least 38 months, avelumab maintenance therapy prolonged OS across all prespecified subgroups, including those who had a complete response (CR; n = 179), partial response (PR; n = 326), or stable disease (SD; n = 195) after 2 or more years of chemotherapy. With avelumab, the median OS was 39.8 months in those with a CR, 19.2 months in those with a PR, and 22.3 months in those with SD. With BSC alone, the median OS was 26.8 months, 12.8 months, and 14.0 months, respectively.

“In essence, this [study] provides level one evidence that avelumab maintenance after platinum-based chemotherapy in patients who don’t progress is a very effective option,” said Gupta, who is the director of genitourinary medical oncology at Taussig Cancer Institute, and co-leader of the Genitourinary Oncology Program at Cleveland Clinic, in Cleveland, Ohio.

In an interview with OncLive^®, Gupta discussed the significance of the phase 3 JAVELIN Bladder 100 trial in urothelial cancer, updated data on the use of avelumab maintenance therapy following first-line chemotherapy in this population, and how this research could better inform patient-provider conversations about this option in the clinic.

OncLive^®: Please provide some background on the JAVELIN Bladder 100 trial, including its purpose and the trial design?

Gupta: JAVELIN Bladder 100 was a pivotal study. It was a 700-patient study [looking] at [whether] maintenance avelumab when added to BSC could improve OS compared with BSC [alone] in patients with locally advanced or metastatic urothelial cancer. [Patients had previously] received first-line platinum-based chemotherapy [consisting of] gemcitabine and cisplatin or gemcitabine and carboplatin and did not progress. Patients who had CRs, PRs, or SD were randomized to avelumab and BSC vs BSC alone within 4 to 10 weeks of completing chemotherapy.

Could you expand on the significance of the primary results from this study? How did they affect the SOC in the frontline setting?

With the prior SOC, if patients had a response after [receiving] 4 to 6 cycles of platinum-based chemotherapy, we would not do anything. If they progressed, we would use immunotherapy in the second-line setting, which improves survival.

When we moved avelumab maintenance into the space where patients did not progress, we [saw] a higher magnitude of benefit. We’ve also seen that in urothelial cancer, adding up-front immunotherapy to chemotherapy is not better than [using] chemotherapy alone. As such, the switch maintenance approach is a very effective approach in urothelial cancer.

The other important aspect is that there’s a lot of drop out for subsequent-line therapies and even approved therapies are not utilized the way they [should be]. Therefore, maximizing the frontline treatment space to improve outcomes is really important.

What findings from this study were presented at this year’s meeting, and why was it important to evaluate long-term patient responses?

In the JAVELIN Bladder 100 study, [we saw that] avelumab [plus] BSC led to a [median] OS of around 21 months compared with around 14 months with BSC alone. [After] at least 38 months of median follow-up, we found that the survival benefit was maintained. It was more pronounced for patients who had CRs to platinum-based chemotherapy, followed by those with PRs, followed by those who had SD.

The bottom line is that all patients benefited [from avelumab maintenance therapy], and the extent of benefit was [greater] in those who had CRs to platinum-based chemotherapy. The same [result] was [observed] for PFS, as well. There were no long-term toxicities [observed] that we have not seen before with avelumab, and [the regimen’s] safety was in line with the prior reports.

How can these data on the magnitude of benefit amongst complete or partial responders be incorporated into discussions with patients in clinical practice?

It is expected that patients who benefit from frontline therapies will probably leverage more with immunotherapy. The way we talk to patients is [by telling them that] platinum-based chemotherapy is still a [standard] frontline therapeutic option. Even if SD is their best response, they’ll [still] benefit from maintenance avelumab. However, many patients who have a CR [will wonder], “Why do we need any more therapy?” [This study provides] evidence that those patients will benefit more from maintenance immunotherapy even though they have no evident disease.

References

1. Valderrama B, Powles T, Sridhar S, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy. J Urol. 2023;209(4):e244. doi:10.1097/JU.0000000000003240.10.
2. FDA approves avelumab for urothelial carcinoma maintenance treatment. FDA. June 30, 2020. Accessed May 9, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment