
Venugopal P
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24 Nov 2024 01:27:43 PMEnfortumab Vedotin for Urothelial Carcinoma
Dear All,
Man’s Desire to live a few days longer is
well known and it plays a pivotal role in Drug Development. The financial
Toxicity associated with such treatments is often ignored and in a country like
India, it is a real concern.
Urothelial Ca has emerged from its ‘Orphaned
State’ to one of the most researched cancer among GU Cancers and the numerous
avenues now being opened appears far more than P Ca. It is true that treatment
of Urothelial Ca is much higher than most of the GU Cancers.
At one time we had only Cisplatin based
therapies for MIBC but today we have diverse drugs for MIBC, be it for primary
Tt (Adjuvant or Neoadjuvant) or as 2nd or even 3rd line
therapies due to failure or unresponsiveness of other therapies.
Immune Checkpoint Inhibitors (ICIs) are
considered as effective treatment for MIBC (both PD-1 and PD-L1) and started
with its use as 2nd line treatment for failed first line with
Cisplatin based treatments. But it soon found its niche in Cisplatin Ineligible
Scenario. Some researchers observed the usefulness of ICIs in the primary
setting and began using it as Neoadjuvant for Trimodality Bladder Sparing
Regimes.
But it was soon found that even ICIs could
be unresponsive in many and treatments with ICIs were only resulting in financial
drain.
This has made Researchers to explore many
other avenues and have come out with antibody-drug conjugate enfortumab vedotin-ejfv
(PadcevTM). Antibody-drug conjugates (ADCs) deliver potent cytotoxic agents using
highly selective monoclonal antibodies. Targeting the near-universal expression
of Nectin-4 on UC cells is a viable therapeutic strategy.
On December 18, 2019, the
antibody-drug conjugate enfortumab vedotin-ejfv (PadcevTM) was
granted accelerated approval for the treatment of adult patients with locally
advanced or metastatic urothelial cancer who have previously received a
programmed cell death protein 1 (PD-1) or programmed cell death ligand 1
(PD-L1) inhibitor and platinum-containing chemotherapy in the
neoadjuvant/adjuvant, locally advanced, or metastatic setting.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784850/pdf/JCO.19.01140.pdf
and Another article in PDF format
EV demonstrated
an overall response rate of 44%, and a median duration of response of 7.6
months. Estimated overall survival was 11.7 months with a median estimated
progression-free survival of 5.6 months.
The dosage schedule recommended is Enfortumab Vedotin-ejfv at 1.25 mg/kg on
days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable
toxicity.
EV, a
first-in-class anti-Nectin-4 ADC, provides impressive response rates with
manageable toxicities, making it a promising treatment option for patients with
multiply relapsed or refractory UC.
The US Food and
Drug Administration-approved EV demonstrate antitumor activity in heavily pre-treated
patients with UC but harbours important adverse effects and financial concerns.
Though
mentioned as Manageable Toxicity, studies have found, Serious adverse events
occurred in 46% of patients, with the most common being urinary tract
infection, cellulitis, febrile neutropenia, diarrhea, sepsis, acute kidney
injury, dyspnea, and rash. Adverse events led to dose interruption in 64%, most
commonly due to peripheral neuropathy, rash, and fatigue, and to dose reduction
in 34%, most commonly due to peripheral neuropathy, rash, and fatigue. Adverse
events led to treatment discontinuation in 16% of patients, most commonly due
to peripheral neuropathy. Fatal adverse events occurred in 3.2% of patients,
including acute respiratory failure, aspiration pneumonia, cardiac disorder,
and sepsis.
Further
development of EV continues in a phase III trial examining EV plus Pembrolizumab
with or without platinum compared with conventional platinum-based
chemotherapy.
There is a likelihood that many more drugs will emerge and change our
pattern of treatments but how much will become the way we treat in India should
be explored. We have a tendency to ape the West and declare what is offered in
the West should be palatable for us in India.
With warm Regards,
Venu
Comments(3)
-
Venugopal P
13 Nov 2020 09:04:46 AMDear All,
In continuation of the previous two write ups and Articles, I am providing another set of articles addressing Emerging and emerged New Treatment options for MIBC. Of late Immune Check Point Inhibitors (ICIs) are being projected as Major advancement for MIBC but it has its own limitations. Ideally, ICIs are administered only after knowing PD-L1 expression positivity. Each drug appears to have its own expression.
Two newer Molecules have been discussed in the Documents provided. But to understand more regarding the various molecules that have arrived or arriving are necessary for us to have some knowledge as what the future may offer for these unfortunates with MIBC.
I am proving you 4 reading materials which I have gathered from many available to enable us to understand the various progresses made in Chemotherapeutics as well as ICIs and beyond.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295780/pdf/10.1177_1756287218814100.pdf
http://tcr.amegroups.com/article/view/13775/html (PDF available)
https://journals.sagepub.com/doi/pdf/10.1177/1078155220971026
https://www.nejm.org/doi/pdf/10.1056/NEJMoa1817323?articleTools=true
Understanding these newer options will take all of us forward and will be of benefit the trainees in our group for furtherance of their knowledge.
With warm regards,
Venu
-
Venugopal P
13 Nov 2020 09:16:23 AMAs the first Link provided may not open, I am providing alternate link for the same article
https://journals.sagepub.com/doi/pdf/10.1177/1756287218814100
Venu
Venugopal P
25 Sep 2020 10:31:46 AMDear All,
In continuation of the previous write up, there are several new molecules being developed for Advanced/metastatic U Ca and I am posting two studies addressing two other agents.
Though these may not be in use in our country for a while, it is also possible that we will begin hearing about these from our pundits sooner than later.
I have provided the information regarding these products as an attachment for your reading. I do not know how much of these are going to be beneficial for us but it is better to know the happenings around us than being ignorant.
With warm Regards
Venu
View Document