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At this year's annual meeting of the American Society of Clinical Oncology (ASCO 2014), held May 30 through June 3 in Chicago, specialists discussed the latest cancer research. The editors of NEJM Journal Watch Oncology and Hematology were on hand to cover key presentations at the conference. Here, Robert Dreicer, MD, MS, FACP, reviews new findings in genitourinary cancer.
In a US Intergroup phase III trial (abstract LBA2), Sweeney and colleagues asked a simple question: Given that docetaxel has the ability to modestly improve survival in the castration-resistant metastatic setting, might it work better earlier in the disease?
To determine the answer, the investigators randomized 790 men (median age, 63) with metastatic prostate cancer not previously treated with androgen-deprivation therapy (ADT) to ADT alone or ADT plus six cycles of docetaxel administered at standard doses every 3 weeks. Patients were well balanced according to stratification factors, including high- or low-volume disease. High-volume disease was defined as the presence of visceral metastases or ≥4 bone metastases (≥1 beyond the pelvis and vertebral column). Two thirds of patients had high-volume disease; three quarters had no prior local therapy
At median follow-up of 29 months, median overall survival (OS; the primary endpoint) improved with docetaxel from 44.0 to 57.6 months (hazard ratio, 0.61; P=0.0003). Improvement in OS was due to a decrease in prostate cancer deaths. In patients with high-volume disease, median OS improved from 32.2 to 49.2 months (HR 0.60; P=0.0006). Data from patients with low-volume disease remain premature. Docetaxel was well tolerated with typical adverse effects.
The data from this large, prospective study establish that in patients with high-volume disease, docetaxel administered for six cycles in combination with ADT is the new standard of care. The role of chemohormonal therapy in patients with lower-risk disease remains undefined.
The management of advanced urothelial bladder cancer has changed little during the past 25 years. Cisplatin-based chemotherapy has the potential to cure a small subset of patients, primarily those with nodal metastases and good performance status and renal function. In early phase I trials of PD-L1 and PD-1 inhibitors, intriguing activity was seen in heavily pretreated patients with urothelial cancer.
Now, Powles and colleagues have conducted an industry-sponsored, multinational, phase I study (abstract 5011) of the PD-L1 inhibitor MPDL3280A. The agent was administered intravenously at a dose of 15 mg/kg every 3 weeks for up to 1 year. Currently, 32 patients (median age, 66) have been treated; 75% had evidence of visceral metastases, and 79% had received prior platinum-based chemotherapy.
Therapy was well tolerated, with rare grade 3 or 4 toxicity and no pneumonitis, renal toxicity, or grade 4 or 5 toxicity. Patients whose tumors demonstrated 2 or 3+ immunohistochemical expression of PD-L1 exhibited a 43% objective response rate. Of interest, even in patients with 1+ or no PD-L1 expression, an 11% objective response rate was seen.
Although the numbers remain small, the degree of clinical activity in a heavily pretreated patient population is remarkable given the current state of limited therapeutics. The potential to treat an older population with a renal-sparing, well-tolerated therapy is potentially paradigm-shifting. A large, multicenter, phase II trial of this agent is now open.
Therapeutic advances in the management of advanced renal cancer from the integration of tyrosine kinase and mTor inhibitors have improved the outcome of many patients. However, these advances mainly benefit those with clear-cell disease, which represents about 85% of the renal cancer population. In some trials, small subsets of patients with non–clear-cell histologies have typically demonstrated a small chance of response and a briefer duration of benefit.
To further evaluate treatment response in patients with non–clear-cell disease, academic investigators have conducted a randomized, phase II trial, with a crossover design (abstract 4505) to compare the effectiveness of first-line everolimus versus sunitinib. Both agents were administered in their standard doses and schedules. During a 3-year period, 68 eligible and evaluable patients were enrolled, most of whom had papillary histology and were considered intermediate risk, using Memorial Sloan Kettering criteria.
Objective response was similar with everolimus or sunitinib therapy (1 and 2 partial responses, respectively). Progression-free survival (the primary endpoint) was also similar (4.1 and 6.1 months), as was overall survival (14.9 and 16.2 months). Toxicity with these agents was as expected. Although a small trend in improvement in outcome was seen with sunitinib, effective first-line treatment for non–clear-cell renal cancer remains an unmet clinical need. Enrollment in ongoing phase II trials of novel agents is imperative.