Senthil Kumar: Metastatic Urothelial Carcinoma – First line therapies
Senthil Kumar, Medical Oncologist at Red Hills, shared a post on X:
“Metastatic Urothelial Carcinoma: First line therapies
Urothelial cancer (UC) ranks as the 10th most common cancer worldwide, with advanced treatment regimens reshaping care standards. Here’s a detailed comparison of current regimens, their benefits, and challenges:
First-Line Therapies
EV-302 Regimen
Enfortumab Vedotin (EV) + Pembrolizumab:
Overall Survival (OS): 32 months (doubled vs chemo: 16 months).
Progression-Free Survival (PFS): 12 months (doubled vs chemo: 6 months).
Overall Response Rate (ORR): 68%.
Challenges:
Cost: Extremely high; EV given until progression further amplifies expense.
Toxicity: Severe and permanent neurotoxicity risk.
Standard arm concerns: Most cases lacked maintenance avelumab.
Next best regimen — concurrent chemo+immuno combo
Checkmate 901 (CM-901)
Nivolumab (Nivo) + Chemo:
OS: 22 months (vs 19 months with chemo).
Deep, durable responses: Especially in lymph-node-only metastasis.
Complete Response (CR): 22%, with some responses lasting 3 years!
Fast & durable responses: Chemotherapy ensures rapid response, while nivolumab extends durability.
Sequential chemo – immuno combo
Platinum Doublet + Maintenance Avelumab (JAVELIN Bladder 100 Trial)
JAVELIN Bladder 100 Trial:
– OS: 24 months (vs 15 months).
– PFS: 5.5 months (vs 2 months).
Sequential vs Concurrent Chemo immuno Therapy ( CM 901 VS JAVELIN BLADDER 100)
No head on comparisons available
For patients unable to afford targeted therapy / immunotherapy
Chemotherapy Regimens
MVAC (Methotrexate + Vinblastine + Doxorubicin + Cisplatin)
OS: 13 months.
PFS: 10 months.
ORR: 40%.
Dose-Dense MVAC (DD-MVAC):
– No significant OS advantage over standard MVAC.
PGC (Triplet: Cisplatin + Gemcitabine + Paclitaxel)
ORR: 56% (better than doublets).
PFS: 8 months.
OS: 16 months.
Platinum Doublet (Cisplatin + Gemcitabine)
OS: 15 months.
ORR: 40-50%.
Cisplatin ineligible patients
Carboplatin-Gemcitabine, EV-302 regimen or Gemcitabine-Paclitaxel.
Platinum-Ineligible patients :
Immunotherapy (e.g., Pembrolizumab) or single-agent chemotherapy.
Immunotherapy Insights
Only EV 302, CM 901 – positive
Other Combination chemo + immunotherapy trials – negative
Trials like KN-361, DANUBE, IMvigor 130, and IMvigor 210 did not show significant OS benefit over chemotherapy alone.
Insights & Takeaways
EV-302 is the new SOC, offering remarkable survival benefits but comes with significant cost and some neuro toxicity.
CM-901 is the next best alternative with durable and deep responses, particularly in lymph-node-only metastasis.
22% CR rate, with many responses lasting 3 years.
Platinum Doublet + Avelumab Maintenance (JAVELIN Bladder 100 Trial) is a strong option with proven survival benefits.
MVAC and PGC are still good regimens for cisplatin-eligible patients, not affordable for the latest therapies
Immunotherapy or non-platinum single agent chemo offers hope for platinum-ineligible patients.”
-
ESMO 2024 Congress
September 13-17, 2024
-
ASCO Annual Meeting
May 30 - June 4, 2024
-
Yvonne Award 2024
May 31, 2024
-
OncoThon 2024, Online
Feb. 15, 2024
-
Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023