bladder cancer 2022 

Awesome lectures brief yet encapsulates all the important points

👍 very well explained

BCG refractory non-muscle invasive bladder cancer Can be treated with Pembrilozumab immunotherapy (FDA approved in 2020). However the response rate is low at about 20%. Otherwise these patients need cystectomy

Enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) is being called the new standard of care for the upfront treatment of locally advanced/metastatic urothelial carcinoma, regardless of PD-L1, Cisplatin-ineligibility, or presence of visceral metastasis. It means that platinum chemotherapy is not the first line, but the second line therapy. www.annalsofoncology.org/article/S0923-7534(23)04270-9/fulltext EV-302/Keynote A39, a phase 3 trial was presented at the 2023 European Society for Medical Oncology annual meeting. The combination soundly beat the current standard of care - platinum-based chemotherapy - with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).

Lymph node (N) staging: I saw many people still use old lymph node staging. But the N staging is not only depending on the number or size but also on the location. In the 2017 TNM staging system, a single lymph node metastasis in the true pelvis is considered N1 disease, multiple nodes in the true pelvis are classified as N2 disease, and nodal involvement of the common iliac nodes is classified as a secondary lymphatic drainage area (N3) rather than metastatic disease. Lymph node sampling should include excision of an average of >12 lymph nodes

December 16, 2022 The US Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer. The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy. Patients with BCG-unresponsive disease have historically had limited treatment options other than bladder removal surgery or pembrilozumab immunotherapy (ORR 20%). Nadofaragene firadenovec-vncg is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein. Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

- Urothelial carcinoma- In CheckMate 901, nivolumab was added to chemotherapy: With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171). It's the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma. However, when compared with pembrolizumab + enfortumab vedotin, the overall survival seems to be shorter. www.annalsofoncology.org/article/S0923-7534(23)04271-0/fulltext

Enfortumab vedotin + Pembrolizumab approved for 1st line therapy for metastatic urothelial cancer: On April 3, 2023, the Food and Drug Administration granted accelerated approval to enfortumab vedotin-ejfv (Padcev) with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy based on KEYNOTE-869 study. A total of 121 patients received enfortumab vedotin-ejfv plus pembrolizumab. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) determined by blinded independent central review using RECIST v1.1. The confirmed ORR in 121 patients was 68% (95% CI: 59, 76), including 12% with complete responses. The median DoR for the dose escalation cohort + Cohort A was 22 months (range: 1+ to 46+) and for Cohort K was not reached (range: 1 to 24+). The most common adverse reactions (>20%), including laboratory abnormalities, were increased glucose, increased aspartate aminotransferase, rash, decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased lymphocytes, fatigue, increased alanine aminotransferase, decreased sodium, increased lipase, decreased albumin, alopecia, decreased phosphate, decreased weight, diarrhea, pruritus, decreased appetite, nausea, dysgeusia, decreased potassium, decreased neutrophils, urinary tract infection, constipation, potassium increased, calcium increased, peripheral edema, dry eye, dizziness, arthralgia, and dry skin. The recommended enfortumab vedotin-ejfv dose when given with pembrolizumab is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) administered as an intravenous infusion over 30 minutes on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. The recommended pembrolizumab dose, administered after enfortumab vedotin on the same day, is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.