Frontline Avelumab Maintenance Displays Long-Term Benefit in Advanced Urothelial Carcinoma

Jeanny B. Aragon-Ching, MD, FACP, discusses the results of the subgroup analysis in patients with urothelial carcinoma who received frontline avelumab maintenance for at least 12 months on the phase 3 JAVELIN Bladder 100 trial.

The findings from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) have established avelumab (Bavencio) maintenance following chemotherapy as the standard of care in the frontline setting for advanced urothelial carcinoma, and future clinical trials evaluating other regimens should feature control arms with avelumab maintenance, according to Jeanny B. Aragon-Ching, MD, FACP.

Primary findings from the study demonstrated that frontline avelumab maintenance plus best supportive care (BSC) elicited overall survival (OS) and progression-free survival (PFS) benefits vs BSC alone in patients with advanced urothelial carcinoma who achieved a response or stable disease following frontline chemotherapy.

Findings from a subgroup analysis of the trial, which were presented at the 2022 ESMO Congress, showed that at a median follow-up of 38 months, 118 of 350 patients in the avelumab arm (33.7%) received a minimum of 12 months of treatment. Among these patients, the median OS was not reached (95% CI, 50.9 months–not estimable [NE]), and the median PFS was 26.7 months (95% CI, 19.4-32.2).

“Offering chemotherapy followed by avelumab maintenance remains the standard of care. This should be advocated for most, if not all, patients who are eligible for this treatment,” Aragon-Ching said.

In an interview with OncLive®, Aragon-Ching, clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute, discussed the results of the subgroup analysis in patients who received frontline avelumab maintenance for at least 12 months, what the data mean for the urothelial carcinoma treatment paradigm, and what still needs to be addressed in the space.

OncLive®: Could you provide background on the JAVELIN Bladder 100 trial?

Aragon-Ching: JAVELIN Bladder 100 is a phase 3, international, randomized trial in locally advanced and metastatic urothelial carcinoma. This trial investigated the use of chemotherapy with either gemcitabine/cisplatin or gemcitabine/carboplatin, followed by avelumab maintenance plus BSC compared with BSC [alone].

Only patients who achieved either a complete response [CR], a partial response [PR], or stable disease [following chemotherapy were randomly assigned] on the trial after waiting 4 to 10 weeks.

The trial was positive because it yielded an OS benefit for the intent-to-treat population and the PD-L1 subgroup of patients. In addition, the PFS results were also positive. This led to the FDA approval in the United States of avelumab maintenance after chemotherapy for patients with metastatic urothelial cancer [in June 2020].

Could you expand on the patient population evaluated in the trial?

The patients [randomly assigned] to avelumab maintenance with BSC vs BSC [alone were comparable]. Most patients were male. Visceral metastases were seen in [54.6% of patients in the avelumab arm and 45.4% of patients in the control arm]. Most of the patients received gemcitabine/cisplatin. [More than half of patients in both arms] were PD-L1 positive.

The benefit was not limited just to the PD-L1–positive population of patients, as it spanned across all populations. If patients achieved a CR, PR, or stable disease [following chemotherapy, they benefited from avelumab]. It is important to remember that the patients who developed progression after 4 to 6 cycles of chemotherapy were excluded from the [randomized portion of] the trial. [These characteristics are from] the overall population of patients who went on to the [randomized portion of] JAVELIN Bladder 100.

What methodologies were utilized in the phase 3 trial?

This was an open-label trial meaning that if patients were receiving avelumab maintenance, they knew that they were receiving it. This was important for a lot of the patients, and it was relevant in the subsequent analysis of quality of life that we reported on the trial.

There were some patients who [were randomly assigned] to the BSC arm and were understandably concerned about the outlook and prognosis of their disease.

What results were presented at the 2022 ESMO Congress on patients who received at least 12 months of treatment on the trial?

At the 2022 ESMO Congress, we reported on a subgroup analysis of patients who received treatment for 12 months and beyond. This is an attempt to understand who these patients are, who are long-term responders, and how they did on the study. This was an updated analysis with a median follow-up of 38 months.

We saw that of all the patients who received avelumab, 33.7% were on avelumab maintenance for 12 months and beyond. When we look at the profile of those patients, it was no different than that of those in the overall avelumab arm. It was a similar population [to the overall population]. This was also a very similar population to the responders [to chemotherapy] with regard to CR, PR, and stable disease.

What is striking is that the median OS was not reached [(95% CI, 50.9 months-NE) in patients who received at least 12 months of avelumab maintenance]. Moreover, the median PFS was 26.7 months [95% CI, 19.4-32.2].

Was there anything notable to report regarding safety?

There were no new safety signals. However, I would say that with prolonged follow-up and prolonged treatment with avelumab maintenance, about half of the patients still had treatment-related adverse effects [TRAEs]. However, many of these TRAEs were manageable. The rate of grade 3 or greater immune-related AEs that occurred after at least 12 months of treatment was 4.2% in patients [who received avelumab].

It is important to continue following patients, but we know that treatment with avelumab works, and the label states [that treatment can continue] until progression or excessive toxicity.

What do these data mean for this patient population moving forward?

The impact of the trial resonates with the whole theme of maintenance avelumab treatment. For the patients who fit the eligibility criteria of JAVELIN Bladder 100, chemotherapy is still our best [frontline] treatment option to this day. This includes treatment with gemcitabine/cisplatin or gemcitabine/carboplatin. If patients achieve either a CR, PR, or stable disease, they then go on to maintenance avelumab, and that remains the standard of care.

For those patients able to go through prolonged treatment [with avelumab], they garner a [significant] benefit, which was seen in this latest subgroup analysis of JAVELIN Bladder 100.

How are you hoping that avelumab maintenance will continue to fit into the treatment landscape for patients?

It fits nicely. Maintenance avelumab is a standard of care. That should be advocated for most, if not all, patients who are eligible to receive chemotherapy.

It is important to continue to follow-up with patients for a comprehensive AE profile. Although [AEs] are few and far between, they still do happen. It is important for physicians and patients alike to be vigilant in monitoring for not only benefits and responses, but also AEs.

What are the next steps for advancing the frontline treatment paradigm for locally advanced or metastatic urothelial cancer?

The next step is [to see] if we can do better. We know that [patients can achieve] good responses and good maintenance therapy is available. Although up to one-third of patients are enjoying good responses and a good quality of life with maintenance avelumab, patients still had to leave the trial and were not able to continue with maintenance avelumab, [primarily] due to progression. We must work to fulfill this unmet need in this field.

[Investigators must determine] how we can add on to maintenance avelumab, and there are several studies ongoing to look at the value of additional agents to go with avelumab maintenance therapy.

Clearly, avelumab maintenance should be the standard of care treatment option, even in clinical trials. In a standard-of-care arm, it is not sufficient to use BSC [without avelumab maintenance] as our comparator arm in a lot of these phase 3 clinical trials.


Aragon-Ching JB, Grivas P, Loriot Y, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): results from patients with ≥12 mo of treatment in JAVELIN Bladder 100. Ann Oncol. 2022;33(suppl 7):S1343. doi:10.1016/j.annonc.2022.07.1838