番茄社区

Post hoc analyses presented at the 2021 virtual showed that the overall survival benefit with frontline avelumab (Bavencio) maintenance was sustained across multiple previously unreported subgroups of patients with advanced urothelial cancer.

In this exclusive 番茄社区 video, , of Massachusetts General Hospital Cancer Center in Boston, discusses three of the related post hoc analyses from the trial.

Following is a transcript of his remarks:

My name is Xin Gao, and I'm a medical oncologist at Mass General Cancer Center, where I focus on treatment of cancers of the urinary tract. I'd like to offer some thoughts on some of the research recently presented at the ASCO annual meeting in June 2021, focusing on three related analyses that came out of the phase III JAVELIN Bladder 100 clinical trial.

As a brief background, JAVELIN Bladder 100 is a randomized phase III trial evaluating the use of maintenance immune checkpoint inhibitor avelumab in patients with unresectable locally advanced or metastatic urothelial cancers who did not have disease progression following completion of first-line platinum-based chemotherapy. So that's either cisplatin/gemcitabine [Gemzar] or carboplatin with gemcitabine for four to six cycles.

This study enrolled 700 patients who were randomized one-to-one to either best supportive care alone or with the addition of avelumab IV every 2 weeks.

The trial was previously presented at ASCO in 2020 and published in the , showing a significant disease-free benefit as well as overall survival benefit with maintenance avelumab, with a hazard ratio of 0.69 and median overall survival of 21.4 months versus 14.3 months. This study led to the approvals of maintenance avelumab by the FDA, as well as the EMA [European Medicines Agency].

Now this year, three post hoc analysis of the JAVELIN Bladder 100 trial were presented at the ASCO annual meeting. I think the most interesting and clinically relevant was the presented by Dr. Tom Powles. In this analysis they first looked at the primary location of the tumor, whether it was upper tract or lower tract primary, and overall maintenance avelumab appeared to be beneficial to patients regardless of the location of their primary tumor.

The second evaluation in this analysis was regarding the type of advanced disease, whether it was metastatic or unresectable locally advanced disease prior to chemotherapy, or lymph node only disease post-chemotherapy. And again, it appeared that maintenance avelumab benefited patients, regardless of the type of advanced disease that they had.

The third subgroup looked at patients who had PD-L1 positive tumors and received first-line carboplatin/gemcitabine. And again, the hazard ratio for overall survival here was 0.67, which is on par with the overall population and showed benefit with maintenance avelumab.

And finally molecular subgroups were analyzed for four groups of characteristic gene-expression profiles based on work from the TCGA [The Cancer Genome Atlas]. So that's basal squamous, luminal, luminal infiltrated, and luminal papillary subtypes. And overall maintenance avelumab appeared to be beneficial regardless of the molecular signatures subgroup, with the exception of maybe the luminal subgroup, which had a hazard ratio of 1.01 for overall survival.

But this included a rather small number of patients in this molecular subgroup, and notably the basal subgroup did have higher PD-L1 expression and more CD8-positive cells in the tumor area than other tumor types, while the luminal subtype of tumors had relatively higher APOBEC [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like] mutagenesis gene signatures.

So I think this clinical and molecular subgroup analysis of JAVELIN Bladder 100 does support the use of maintenance avelumab further in advanced urothelial carcinoma patients who had not progressed after first-line platinum-based chemotherapy, really regardless of any clearly discernible clinical and molecular features benefiting more or less. And perhaps a lone exception is this luminal subtype group of tumors, where additional studies I think are needed given the relatively small numbers of patients in this post hoc analysis.

The second post hoc analysis that was presented at ASCO this year on JAVELIN Bladder 100 was , and the investigators evaluating the time to end of next-line therapy and the randomized trial population.

The endpoint here was time from randomization until the end of next-line treatment received after first progression, either due to death or discontinuation of treatment. This time was significantly longer in the randomized population, with a median time to end of next-line therapy of 14.8 months compared to 9.2 months in favor of maintenance avelumab. This was similar for patients with PD-L1 positive tumors as Ventana ​SP263 assay with a median of 18.1 months versus 9.0 months. Again, favoring maintenance avelumab rather than best supportive care.

And then finally, the third post hoc analysis of JAVELIN Bladder 100 was a , and the investigators looked at the treatment-free interval from the last dose of chemotherapy to the start of maintenance avelumab or best supportive care alone on the study. This ranged from 4 weeks to 10 weeks on the trial.

And the conclusion was that the maintenance avelumab was again beneficial regardless of the treatment-free interval, which was characterized as between 4 and 6 weeks versus 6 to 8 weeks and versus 8 to 10 weeks.

So I think that summation of these three post hoc analyses really adds further support for the use of maintenance avelumab in this population of patients with advanced urothelial carcinoma who did not progress after first-line platinum and gemcitabine-based chemotherapy.

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