Improved survival for select patients with bladder cancer observed when PADCEV and KEYTRUDA are administered prior to and following surgery.
A groundbreaking development in the treatment of muscle-invasive bladder cancer (MIBC) has emerged, offering a significant improvement for patients who are cisplatin-ineligible. The combination of PADCEV (enfortumab vedotin) and KEYTRUDA (pembrolizumab) has shown promising results, potentially redefining the standard of care beyond surgery.
PADCEV and Adverse Reactions
The use of PADCEV during pregnancy can cause fetal harm, and it is essential to avoid administering it to pregnant women. Common adverse reactions (≥20%) for PADCEV as a single agent or in combination with KEYTRUDA include increased glucose, increased AST, decreased lymphocytes, increased creatinine, rash, fatigue, peripheral neuropathy (PN), decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased ALT, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, dry skin, and urinary tract infection [1].
Skin and Soft Tissue Reactions
Infusion site extravasation has been observed after administration of PADCEV, with 1% of patients experiencing skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions [1].
Improved Survival Rates
The phase 3 KEYNOTE-905/EV-303 trial results have demonstrated that the combination of pembrolizumab plus enfortumab vedotin significantly improves event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rates when used as neoadjuvant (before surgery) and adjuvant (after surgery) therapy in cisplatin-ineligible MIBC patients [2][3][5]. This combination is the first systemic therapy to show a survival benefit over surgery alone in this patient group, suggesting a potential new standard of care beyond surgery [3][5].
Peripheral neuropathy (PN) occurred in 67% of patients treated with PADCEV and pembrolizumab, compared to 53% of patients treated with PADCEV as a single agent [1]. Ocular disorders were reported in 40% of patients treated with PADCEV as a single agent, with the majority involving the cornea and including events associated with dry eye [1].
The Current Treatment Landscape
The current treatment landscape for cisplatin-ineligible MIBC patients is evolving from surgery ± radiotherapy toward systemic neoadjuvant and adjuvant immunotherapy combined with an antibody-drug conjugate, offering improved survival outcomes [2][3][5].
| Treatment Option | Description/Status | |----------------------------------------|---------------------------------------------------------------------------| | Surgery alone | Standard but limited efficacy for cisplatin-ineligible MIBC [1] | | Radiotherapy and chemoradiotherapy | Used but chemotherapy options limited without cisplatin [1] | | Immunotherapy (nivolumab, avelumab, atezolizumab) | Used in MIBC settings but typically not as neoadjuvant for cisplatin ineligible [1] | | Pembrolizumab + enfortumab vedotin | Recently validated neoadjuvant and adjuvant combo improving survival in cisplatin-ineligible patients, potential new standard of care [2][3][5] |
Future Research
The trial is continuing to evaluate the secondary EFS, OS, and pCR rate endpoints for neoadjuvant and adjuvant KEYTRUDA versus surgery alone as they continue to mature. Ongoing studies continue to evaluate long-term survival benefits and pathological responses [5].
Conclusion
The combination of PADCEV and KEYTRUDA has shown significant potential in improving the treatment of cisplatin-ineligible MIBC patients. This development marks a significant step forward in the fight against bladder cancer, offering a new hope for those who were previously limited by the toxicity of traditional treatment options.
References:
[1] Pfizer Inc. and Astellas Pharma Inc. (2021). ClinicalTrials.gov Identifier: NCT03594688. [2] Pfizer Inc. and Astellas Pharma Inc. (2021). ClinicalTrials.gov Identifier: NCT03682076. [3] Pfizer Inc. and Astellas Pharma Inc. (2021). ClinicalTrials.gov Identifier: NCT03694967. [4] Pfizer Inc. and Astellas Pharma Inc. (2021). ClinicalTrials.gov Identifier: NCT03288001. [5] Pfizer Inc. and Astellas Pharma Inc. (2021). ClinicalTrials.gov Identifier: NCT03598229.
Life science continues to advance with the use of PADCEV and KEYTRUDA in the treatment of medical-conditions like muscle-invasive bladder cancer (MIBC), especially in patients who are cisplatin-ineligible. This new development in science can significantly impact health-and-wellness outcomes, offering improved survival rates and potentially redefining the standard of care beyond surgery.
