GU Symposium Focuses on Prognostic Model in Urothelial Cancer, Novel Therapies for Prostate and Kidney Cancers


Get Permission

THE 2018 GENITOURINARY Cancers Symposium hosted an international audience of oncologists and other stakeholders to hear about the latest advances in the field. We have included coverage of many of the top news stories from the meeting in previous issues of The ASCO Post. Here are summaries of a few other notable presentations from the meeting. 

Model for Predicting Survival in Urothelial Cancer 

AN OFTEN-STATED unmet need is the emergence of biomarkers to select patients for immunotherapy who are likely to gain benefit from these new, expensive drugs. This need is pressing for those with urothelial cancers, now that five immunotherapies are approved in this setting and about 20% to 25% of patients have long-term responses to these drugs. 

Researchers have developed a preliminary model to predict overall survival in patients with advanced urothelial cancer treated with atezolizumab (Tecentriq) whose cancers have progressed on cisplatin-based therapy. The model was based on data from 310 patients who were enrolled in the phase II IMvigor210 clinical trial and validated in 95 patients with bladder cancer after platinum treatment with atezolizumab in a phase I trial.1 

Gregory Pond, PhD

Gregory Pond, PhD

“We believe we have developed the first prognostic model that, once confirmed in larger studies, could provide a critical decision-making tool for clinicians,” stated lead author Gregory Pond, PhD, of McMaster University, Hamilton, Ontario, Canada. 

In the development of the model, traditional factors were evaluated, as was programmed cell death ligand 1 (PD-L1) status, a potential marker for the efficacy of atezolizumab. Six prognostic factors were identified: Eastern Cooperative Oncology Group (ECOG) performance status, liver metastases, elevated platelet blood count, increased neutrophil-lymphocyte ratio, elevated lactate dehydrogenase level, and hemoglobin < 10 g/dL. 

A linear relationship was observed between the number of factors a patient had and survival. In the IMvigor210 trial cohort, median overall survival was 19.6 months for those with 0 to 1 factors; 5.9 months for those with 2 to 3 factors; and 2.6 months for those with 4 factors or more. 

The authors plan to validate the model in other data sets and try to identify specific subgroups with a preferential response to atezolizumab. 

Use of Docetaxel in Nonmetastatic Advanced Prostate Cancer 

THE LARGE, innovative STAMPEDE trial previously found that using docetaxel in addition to hormonal therapy reduced the risk of recurrence in men with nonmetastatic prostate cancer. A new analysis of the ongoing trial found this strategy also improved quality of life and reduced the need for subsequent therapy, thereby reducing costs.2 

Nicholas D. James, MD, PhD

Nicholas D. James, MD, PhD

“We already knew that docetaxel prolongs survival for men with metastatic prostate cancer, but this improvement in quality of life and reduction in subsequent treatment, and therefore costs, in nonmetastatic disease is somewhat surprising and may cause clinicians to re-think how and when they use docetaxel to treat prostate cancer,” said lead author Nicholas D. James, MD, PhD, of the University of Birmingham, UK. 

The ongoing STAMPEDE trial includes 9,000 men with nonmetastatic and metastatic advanced prostate cancer and to date has evaluated 10 different drugs and therapy alone (standard of care). 

Quality of life was self-reported using EuroQol EQ-5D and included mobility, self-care, activities of daily life, pain levels, and anxiety and depression levels. Based on responses, the authors modeled changes in the predicted length of survival, quality-adjusted life years (QALY), and incremental cost-effectiveness. 

“Improvement in quality of life and reduction in subsequent treatment, and therefore costs, may cause clinicians to re-think how and when they use docetaxel to treat prostate cancer.”
— Nicholas D. James, MD, PhD

Tweet this quote

For men with metastatic disease treated with docetaxel plus hormone therapy, predicted survival was 0.89 years longer than with hormone therapy alone, and quality of life was preserved for 0.51 years longer. For men with nonmetastatic disease, predicted survival was 0.78 years longer and quality of life was preserved for an additional 0.39 years with docetaxel plus hormone therapy vs hormone therapy alone. 

The addition of docetaxel to hormone therapy was cost-effective for both nonmetastatic and metastatic prostate cancers. In the UK, the estimated cost per QALY gained was £5,000 (about $6,750 dollars in the United States). 

In the United States, there is ongoing discussion about the choice between abiraterone (Zytiga; an oral drug) and docetaxel in metastatic and nonmetastatic cancers; docetaxel is about one-fifth of the cost of abiraterone. 

Cabozantinib vs Sunitinib in Metastatic Renal Cell Carcinoma 

IN INTERMEDIATE- or poor-risk previously untreated metastatic renal cell carcinoma, cabozantinib (Cabometyx) improved median progression-free survival from 5.3 months with sunitinib (Sutent) vs 8.6 months with the newer drug, according to an assessment by an independent radiology review committee of the CABOSUN phase II study.3 Cabozantinib reduced the risk of disease progression by 52% in the overall population (P = .0008). The overall response rate was 20% vs 9%, respectively. 

Daniel J. George, MD

Daniel J. George, MD

At the meeting, lead author Daniel J. George, MD, of Duke University, Durham, North Carolina, presented a full subgroup analysis and objective response rates from the phase II trial. All subgroups had a similar benefit from cabozantinib, a drug that is targeted to MET. Subgroups with poor prognostic factors had shorter median progression-free survival with both drugs: 6.8 months for cabozantinib vs 2.7 months for sunitinib. 

“Patients of all risk groups tested benefited from cabozantinib, including patients with favorable-risk features (ie, lower tumor volume, one metastatic organ site) and intermediate- and poor-risk patients,” he continued. Further evaluation is needed to determine which risk groups should receive cabozantinib in the first-line setting. “There is still a trend favoring cabozantinib in MET-negative patients,” Dr. George commented. 

The study included 157 patients randomized 1:1 to receive either drug. About 45% were aged 65 or older, 78% were male, 58% had an ECOG performance status of 1 or 2, 19% had poor-risk disease, and 36% had bone metastasis. MET status was determined in 131 patients, and of them, 47% were MET-positive. 

“We saw a significant shift favoring cabozantinib in MET-positive patients, which validates MET inhibition as a target of cabozantinib and has clinical significance,” Dr. George said. “Patients with MET-positive status had a 68% improvement in progression-free survival, suggesting this negative prognostic factor is a predictive factor for response to cabozantinib.” 

Pazopanib vs Temsirolimus in Metastatic Renal Cell Carcinoma 

THE SMALL, randomized phase II TemPa trial, conducted in a similar patient population as CABOSUN, found that pazopanib (Votrient) was superior to temsirolimus (Torisel) as first-line therapy for intermediate-risk patients by the International Metastatic Renal Cell Carcinoma Database (IMDC) criteria, extending progression-free and overall survival in that group.

Nizar M. Tannir, MD

Nizar M. Tannir, MD

“Pazopanib achieved superior progression-free survival, higher objective response rates, and numerically longer overall survival in intermediate-risk disease. Both agents are ineffective in poor-risk disease. It’s clear that temsirolimus cannot be considered standard of care, even for poor-risk disease,” said lead author Nizar M. Tannir, MD, of MD Anderson Cancer Center, Houston. 

The study had a target accrual of 90 patients but was closed to accrual early when the results of CABOSUN and CheckMate 214 were presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid. Among 69 evaluable patients, the median age was 61 years, 75% were male, and 64% had poor-risk disease. A total of 30 patients (43%) had prior nephrectomy. Thirty-five patients were treated with pazopanib (15 with intermediate-risk disease, 20 with poor-risk disease) and 34 received temsirolimus (10 with intermediate-risk disease and 24 with poor-risk disease). Treatment was continued until disease progression or unacceptable toxicity. At disease progression, crossover to the other treatment was allowed. 

“Pazopanib achieved superior progression-free survival, higher objective response rates, and numerically longer overall survival in intermediate-risk disease.”
— Nizar M. Tannir, MD

Tweet this quote

In the overall study population, the unadjusted median progression-free survival was 5.2 months for pazopanib vs 2.6 months for temsirolimus (hazard ratio [HR] = 0.70; 95% confidence interval [CI] = 0.43–1.14, P = .16). Partial responses were seen in 26% of pazopanib-treated patients and 6% of temsirolimus-treated patients (odds ratio = 5.37, 95% CI = 1.06–27.07, P = .046). 

“A test for interaction showed that pazopanib was favored for response rates and progression-free survival in intermediate-risk patients,” Dr. Tannir told listeners. However, no interaction was found between treatment arm and risk group for overall survival. Median overall survival among all 69 patients was 12 months with pazopanib vs 7.3 months with temsirolimus. 

Adverse events were as expected with each drug. Events more frequently seen with pazopanib included high rates of diarrhea, nausea, and hypertension. For temsirolumus, the most common adverse events were hypertriglyceridemia, anemia, and edema of the limbs. 

“The data from this study suggest temsirolimus is not effective in IMDC intermediate–risk disease and both temsirolimus and pazopanib are not effective in IMDC poor–risk disease. However, pazopanib and sunitinib have a role in favorable-risk patients, and in some patients with intermediate-risk disease,” Dr. Tannir said, during a postpresentation discussion. ■

DISCLOSURE: Drs. Pond, James, George, and Tannir reported no conflicts of interest. 

REFERENCES 

1. Pond GR, Niegisch G, Rosenberg JE, et al: New 6-factor prognostic model for patients with advanced urothelial cancer receiving post-platinum atezolizumab. 2018 Genitourinary Cancers Symposium. Abstract 413. Presented February 9, 2018. 

2. James N, Woods B, Sideris E, et al: Addition of docetaxel to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Long-term survival, quality-adjusted survival, and cost-effectiveness analysis. 2018 Genitourinary Cancers Symposium. Abstract 162. Presented February 8, 2018. 

3. George DJ, Hessel C, Halabi S, et al: Cabozantinib versus sunitinib for previously untreated patients with advanced renal cell carcinoma of intermediate or poor risk: Subgroup analysis of progression-free survival and objective response rate in the Alliance A031203 CABOSUN trial. 2018 Genitourinary Cancers Symposium. Abstract 582. Presented February 10, 2018. 

4. Tannir NM, Ross JA, Devine CE, et al: A randomized phase II trial of pazopanib versus temsirolimus in patients with advanced clear-cell renal cell carcinoma of intermediate and poor-risk (the TemPa trial). 2018 Genitourinary Cancers Symposium. Abstract 583. Presented February 10, 2018.


Advertisement

Advertisement



Advertisement