EAU 2019: Chemotherapy - In a PDL1 Positive Patient with Good Performance Status and GFR with Lung Metastases

Barcelona, Spain (UroToday.com) In the Common Problems in Muscle Invasive and Advanced Bladder Cancer: Evidence-Based Debates session at the 2019 European Association of Urology meeting EAU 2019, Dr. Wassim Kassouf presented the following case to facilitate the debate between Professor Jens Bedke and Dr. Petros Grivas  titled: "In a PDL1 + ve patient, good PS and renal function, with lung metastases, should I use IO (anti PDL1 therapy) as initial therapy instead of chemotherapy?"  The patient case was as follows: 72-year-old man with gross hematuria, with well-controlled hypertension, and otherwise healthy (ECOG PS 0, eGFR 70 ml/min, no neuropathy or hearing loss, no CHF). His workup revealed a large bladder mass invading the prostate with pelvic and retroperitoneal lymphadenopathy; a CT of the thorax demonstrated bilateral lung nodules consistent with metastases. A TURBT showed muscle-invasive high-grade urothelial carcinoma, PD-L1 positive.

Dr. Jens Bedke started the discussion by making the point that first line chemotherapy is the best option for this patient. His first point is that chemotherapy is effective. von der Maase et al.1 reported on 405 patients with metastatic urothelial carcinoma randomized 1:1 to receive gemcitabine/cisplatin or standard MVAC every 28 days for a maximum of six cycles. Overall survival was similar in both arms (HR 1.04, 95%CI 0.82-1.32), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI 0.72 to 1.10), and response rate (gemcitabine/cisplatin 49%; MVAC 46%). More gemcitabine/cisplatin patients completed six cycles of therapy, with fewer dose adjustments; toxic death rate was 1% in the gemcitabine/cisplatin arm and 3% in the MVAC arm.

Secondly, Dr. Bedke notes that chemotherapy is durable. In an update of the previous gemcitabine/cisplatin vs MVAC trial1, 347 patients had died (gemcitabine/cisplatin arm 176 patients; MVAC arm 171 patients) 2 and overall survival was similar in both arms (HR 1.09. 95%CI 0.88-1.34) with a median survival of 14.0 months for gemcitabine/cisplatin and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (p = 0.53). The median progression-free survival was 7.7 months for gemcitabine/cisplatin and 8.3 months for MVAC, with an HR of 1.09; 5-year progression-free survival rates were 9.8% and 11.3%, respectively (p = 0.63).

Third, Dr. Bedke states that chemotherapy has established risk groups, including the Bajorin and Bellmunt risk factors. Among 203 patients with metastatic disease, Bajorin et al. [3] found that Karnofsky performance status (KPS) less than 80% and visceral (lung, liver, or bone) metastasis were high-risk factors. Median survival times for patients who had zero, one, or two risk factors were 33, 13.4, and 9.3 months, respectively (p = 0.0001). Among 156 patients with metastatic disease, Sengelov et al.4 found that good performance status, normal alkaline phosphatase, an absence of liver metastases and chemotherapy were independent prognostic factors for long survival.

Finally, Dr. Bedke noted that chemotherapy is cost-effective. A previous cost-utility of gemcitabine/cisplatin versus MVAC found that the mean incremental cost of gemcitabine/cisplatin over MVAC was estimated to be approximately £2,976 per patient, based on a mean of 4.65 cycles per patient treated with gemcitabine/cisplatin compared with a mean of 3.92 cycles per MVAC patient5. When combined with utility estimates, this resulted in an incremental cost-effectiveness ratio of approximately £22,925 per quality-adjusted life year gained associated with the choice of gemcitabine/cisplatin over MVAC. Dr. Bedke notes that in Germany in 2019, cisplatin only costs €80 (100 mg) and gemcitabine €150 (1000 mg).

Presented by: Wassim Kassouf, Professor, Department of Surgery in Urology, McGill University, Montreal Canada and Professor Jens Bedke, Department of Urology, Eberhard Karls University Tübingen, Tuebingen, Germany

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia Twitter: @zklaassen_md at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona Spain, March 15-19, 2019.

References:
  1. Von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000 Sep;18(17):3068-3077.
  2. von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-4608.
  3. Bajorin DF, Dodd PM, Mazumdar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 1999 Oct;17(10):3173-3181.
  4. Sengelov L, Kamby C, von der Maase H. Metastatic urothelial cancer: evaluation of prognostic factors and change in prognosis during the last twenty years. Eur Urol. 2001 Jun;39(6):634-642.
  5. Robinson P, Maase HV, Bhalla S, et al. Cost-utility analysis of the GC versus MVAC regimens for the treatment of locally advanced or metastatic bladder cancer. Expert Rev Pharmacoecon Res. 2004 Feb;4(1):27-38.
Read the Opposing Argument:
Immunotherapy - In a PDL1 Positive Patient with Good Performance Status and GFR with Lung Metastases
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