Thomas Hutson D.O.

Rini, B. I., D. F. McDermott, H. Hammers, W. Bro, R. M. Bukowski, B. Faba, J. Faba, R. A. Figlin, T. Hutson, E. Jonasch, R. W. Joseph, B. C. Leibovich, T. Olencki, A. J. Pantuck, D. I. Quinn, V. Seery, M. H. Voss, C. G. Wood, L. S. Wood and M. B. Atkins (2016). “Society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma.” J Immunother Cancer 4: 81.

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Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR). Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors, is emerging and will play a significant role in the treatment of patients with RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task Force, which met to consider the current role of approved immunotherapy agents in RCC, to provide guidance to practicing clinicians by developing consensus recommendations and to set the stage for future immunotherapeutic developments in RCC.

Vogelzang, N. J., K. Fizazi, J. M. Burke, R. De Wit, J. Bellmunt, T. E. Hutson, E. Crane, W. R. Berry, K. Doner, J. D. Hainsworth, P. J. Wiechno, K. Liu, M. F. Waldman, A. Gandhi, D. Barton, U. Jungnelius, A. Fandi, C. N. Sternberg and D. P. Petrylak (2016). “Circulating tumor cells in a phase 3 study of docetaxel and prednisone with or without lenalidomide in metastatic castration-resistant prostate cancer.” Eur Urol: 2016 Aug [Epub ahead of print].

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Elevated circulating tumor cell (CTC) blood levels (>/=5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients. Baseline CTCs were <5 cells/7.5ml blood in 87 (42%) patients and >/=5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count >/=5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to >/=5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from >/=5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003). PATIENT SUMMARY: Our study in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.

Sternberg, C., A. Armstrong, R. Pili, S. Ng, R. Huddart, N. Agarwal, D. Khvorostenko, O. Lyulko, A. Brize, N. Vogelzang, R. Delva, M. Harza, A. Thanos, N. James, P. Werbrouck, M. Bogemann, T. Hutson, P. Milecki, S. Chowdhury, E. Gallardo, G. Schwartsmann, J. C. Pouget, F. Baton, T. Nederman, H. Tuvesson and M. Carducci (2016). “Randomized, double-blind, placebo-controlled phase iii study of tasquinimod in men with metastatic castration-resistant prostate cancer.” J Clin Oncol: 2016 June [Epub ahead of print].

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PURPOSE: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. PATIENTS AND METHODS: Men with chemotherapy-naive mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. RESULTS: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status >/= 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade >/= 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. CONCLUSION: In chemotherapy-naive men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Hutson, T. E., G. R. Thoreson, R. A. Figlin and B. I. Rini (2016). “The evolution of systemic therapy in metastatic renal cell carcinoma.” Am Soc Clin Oncol Educ Book 35: 113-117.

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The treatment landscape for renal cell carcinoma (RCC) is a dynamic process that has seen considerable change in recent years. We have seen a rebirth of original breakthroughs with immune checkpoint inhibitors showing promise in patients with treatment-refractory disease. The optimal sequencing of treatments and incorporation of novel therapeutics are actively being investigated and have yet to be determined. The clinical challenges of this evolving treatment paradigm can be attributed to cost considerations, toxicity, and defining endpoints in the management of advanced RCC. As novel therapeutics emerge, finding the optimal treatment regimen for patients will have an increasing focus on patient-centered outcomes and improvement in quality of life in addition to improving survival.

Porta, C., G. Tortora, J. M. Larkin and T. E. Hutson (2016). “Management of poor-risk metastatic renal cell carcinoma: current approaches, the role of temsirolimus and future directions.” Future Oncol 12(4): 533-549.

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Targeted therapies have substantially improved outcomes in metastatic renal cell carcinoma (mRCC). As expected, poor-risk patients have the worst outcomes. Temsirolimus is currently the only agent licensed for treatment of poor-risk mRCC patients. It is associated with meaningful improvements in survival and quality of life, highlighting the importance of correctly stratifying risk in mRCC patients so they receive optimal treatment. Currently, data for other targeted therapies in poor-risk patients are relatively sparse. Optimizing outcomes in these patients is the subject of ongoing research, including studies of biomarkers and studies to elucidate the role of nephrectomy and neoadjuvant targeted therapy in poor-risk mRCC patients. The impacts of novel combinations including temsirolimus have also been explored to further improve outcomes.