NEW YORK – It’s been three years since the US Food and Drug Administration agreed Janssen’s Balversa (erdafitinib) for patients with advanced bladder tumors harboring FGFR3 or FGFR2 gene alterations, however a recent analysis showed that uptake of targeted therapy was very low.
In a retrospective analysis published last week in gamma tumors, University of Pennsylvania researchers found that only 45 percent of 761 urological cancer patients previously treated in the real-world Flatiron Health database were tested for FGFR alterations. The researchers retrospectively analyzed patient data from 2016 through mid-2021.
The low biomarker test rate wasn’t the only reason researchers cited for Balversa’s low absorption, though. Of the patients who underwent biomarker testing and were positive for FGFR alterations, only 42.3 percent went on to receive targeted therapy.
“We expected that there would be rapid uptake of the drug in eligible patients given the enthusiasm for precision medicine and the drug’s efficacy in the phase II study,” said Vivek Nimjaonkar, an associate graduate of the Penn Center for Precision Medicine and one of the authors. In the study. “We were surprised to find that less than half of those with sensitive changes received erdafitinib.”
The U.S. Food and Drug Administration granted Balversa expedited approval in 2019 for previously treated advanced bladder cancer based on a Second stage study It turns out to be effective Shrinking tumors In 40 percent of patients with changes in FGFR2/3, including mutations and fusions. Agency approved Therascreen Qiagen FGFR RGQ RT-PCR kit as a companion diagnosis to identify patients eligible for Balversa. There are also next generation sequencing board tests on the market that can detect FGFR2/3 changes.
To put the low uptake in context, Nimgaonkar and fellow UPenn researchers, including co-lead authors Erica Carpenter, director of the Metastatic Tumor Materials Laboratory at UPenn, and Ronak Mamtani, associate professor at UPenn, compared the rates of advanced bladder cancer patients who received treatment. Genentech Tecentriq’s immune checkpoint inhibitor (atezolizumab) after its approval in 2016. Notably, the efficacy of immunotherapy in this patient population was subsequently called into question, and Genentech voluntarily withdrew its expedited approval request in 2021 — near the end of the real world data. Analysis period – When medication does not end up improving overall survival in confirmatory trials.
Balversa’s rapid approval in 2019 was based on the response rate in One arm trial, and not on the basis of an overall survival advantage, which could affect its uptake. However, Tecentriq was also granted expedited approval without comprehensive survival data, and according to real-world data analysis, its uptake was significantly faster than Balversa within six months of accelerated approval in a second-line setting. Nearly three-quarters of eligible bladder cancer patients received this drug in the half-year after it was approved, compared to less than half of eligible patients receiving the targeted therapy.
While Nimgaonkar stressed that UPenn’s analysis was not designed to identify the root causes of Balversa uptake was significantly lower than that of Tecentriq, it has been suggested that a lack of biomarker testing is required to determine treatment eligibility, in addition to the more acceptable toxicity profile. , he might be playing.
“There are significant side effects associated with erdafitinib, which are unique,” he said, citing side effects such as blurred vision and rashes.
There are financial implications as well. According to Nimgaonkar and colleagues, Balversa costs more than $20,000 per month, which is a major drawback for patients despite the fact that Janssen offers financial assistance programs. According to reports published when Tecentriq was available for bladder cancer, the immunotherapy cost about $12,500 per month. The study authors were unwilling to comment on the extent to which insurance companies were willing to cover the Balversa biomarker test and FGFR. However, patients’ access to biomarker-based therapies can be restricted Reluctance of defenders to cover Large NGS tumor profiling panels are increasingly being used to personalize care.
Despite these drawbacks, Nimgaonkar noted that real-world overall survival rates among Balversa-treated patients mirrored those of the Phase II study group, demonstrating its benefit for these patients. In the clinical trial leading to approval of the drug, median overall survival was 10.5 months compared to 8.97 months for those who received Balversa in the real-world database, which was not a statistically significant difference. He added that this is not something that can be said for every drug; Survival rates in the real world are often worse than those seen in clinical trials.
This confirms how surprising these results are [showing low uptake] Because it indicates that the drug offers efficacy similar to that seen in the clinical trial that prompted FDA approval.”
Access to a vital signs test
While the authors suspect that adverse events, toxicities, and lack of phase III data may play a role in the decreased absorption among eligible patients, there are other barriers to date when it comes to identifying which patients in the first place are eligible.
The authors cited limited awareness, limited interpretation of test results, and concerns surrounding test response times as factors that may play a role in low FGFR biomarker test rates. Tissue insufficiency, which precludes biomarker testing, may also play a role, although the authors are quick to note that liquid biopsies have been used to test about one-fifth of patients for FGFR biomarkers in the Flatiron Health database, and that this depends on blood can That the alternative would at least help address the barriers to tissue testing, if properly validated.
“Interestingly, in this study, we found that blood-based tests for FGFR alterations were successful in identifying many FGFR changes when tissues were not tested,” Carpenter noted. “This suggests that blood-based testing can be used to augment tissue-based testing, particularly in cases where tissue-based testing is limited by tissue deficiency or inability to access archival tissue.”
Going forward, she said, future studies should investigate the concordance between blood-based testing and tissue testing specifically for FGFR alterations in bladder cancer patients. Meanwhile, there are others in the field of them Those at The Ohio State University Comprehensive Cancer Center – GEMSthe use of liquid biopsies to detect FGFR fusion has been revised.
The treatment landscape for advanced bladder cancer has undergone dynamic changes in recent years, with immunotherapy approvals and withdrawals playing a role in greater concerns about the U.S. Food and Drug Administration’s Expedited Approval Program. Accordingly, researchers in Pennsylvania suspect that the confirmed phase III data for palversa can go a long way in helping to improve its absorption.
More studies could also help shed light on the best sequence of treatment, since another non-chemotherapy option is Seagen and Astellas’s Padcev conjugate (enfortumab) also approved for advanced bladder cancer after the first immunotherapy, and Tecentriq may be given first line to some patients who are not platinum-eligible. As such, the best place for Balversa in the sequence of treatments may not be clear to many oncologists.
Going forward, the researchers hope to explore differences in outcomes between patients who had a biomarker test for FGFR and got Balversa, and those who got other treatments. In the current analysis, the researchers did not consider the impact of access disparities by demographics, socioeconomic status, and treatment setting of patients, but they hope to do so in the future.
Source: https://cialiscaps.com/upenn-researchers-found-reduced-absorption-of-janssens-balversa-in-eligible-bladder-cancer-patients/