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2014: What an interesting clinical year in GU oncology!
Why I prefer real data to hype and promissory notes
Surprise! I write this on the eve of a new year, and I want to look back at 2014 through eyes less steely than the Grinch.
In truth, this actually has been a year when a great deal of important work has come to fruition, and the hard core of rational, earnest and careful investigators — who try to produce data to support their views — have shone forth.
I’m going to focus on very important work in cancers of the bladder and prostate.
Derek Raghavan
I do believe that the need for improved treatments for testis cancer remains very important, as I noted in my recent essay in Clinical Cancer Research. But I continue to be irritated by the wastage of resources and repetitive publication of a vast array of data, which are recycling and reinventing of what we know, but with larger numbers, or statistically unproven, so I won’t cite any papers in that field that particularly captured my interest.
Renal carcinoma is in the midst of a halcyon period, with steady improvement, novel therapies and some extraordinarily interesting conceptual trials in progress. Of course, I understand the importance of X-vs.-Y trials — and they abound — but again, I found nothing that I feel compelled to mention here.
Adjuvant chemotherapy in high-risk bladder cancer
Cure obviously is what we so often seek, so let’s start with early-stage disease.
We just saw the publication from the European Organisation for Research and Treatment of Cancer that finally defines a meaningful outcome for their 30994 study, a randomized trial of adjuvant chemotherapy in patients with muscle-invasive bladder cancer.
Truth in disclosure is that these superb investigators — led by Cora N. Sternberg, MD, FACP — designed a strong trial, which should have been supported at least by those who style themselves as academic physicians. But it wasn’t — often because non-academic academicians interfered with the ability of their colleagues to do so.
My pet peeve is when geniuses are happy to see a study designed, but somehow “know” the answer before the study is complete and refuse to play. So, the study closed prematurely.
The investigators tested radical cystectomy vs. radical cystectomy followed by adjuvant MVAC, which consists of methotrexate, vinblastine, doxorubicin (Adriamycin; Pharmacia & Upjohn) and cisplatin.
The initial plan was to have more than 800 accruals, but they had to stop at 288. Results predictably showed substantially improved DFS, and they showed a trend in favor of OS — about 10% different (not the dramatic difference that the mavens had been claiming). This study failed to prove an OS benefit from this treatment, and that is the aim of adjuvant therapy.
The reason that I discount even the benefit listed is that it occurred only in N0, M0 disease. In my book, that sets into question aspects of the surgical work prior to randomization. The study wasn’t designed to ask that question, and I don’t know the answer, but I don’t see evidence that this can set any new standard of care.
ADT with chemotherapy in metastatic prostate cancer
In the domain of metastatic disease, the US Intergroup’s E3805/CHAARTED study was presented at the ASCO Annual Meeting. Please note that this was presented but has not yet been peer reviewed to my knowledge.
This study looked at the role of adjuvant hormone therapy with androgen deprivation therapy (ADT) vs. adjuvant hormone therapy with chemotherapy for patients with hormone-sensitive, newly metastatic prostate cancer. Researchers stratified results by good-risk and poor-risk disease.
For the first time, researchers showed impressive initial figures that demonstrated the utility of the addition of chemotherapy to ADT, but this was limited to patients with poor-risk disease. In that group, median OS was 49.2 months with ADT plus docetaxel vs. 32.2 months with ADT alone (HR=0.6; 95% CI, 0.45-0.81).
This is important as it showed a strong new approach, with powerful differences in survival curves (they didn’t need waterfall plots, and the hazard ratios reflect differences measured in years) for patients with high-risk disease. It also gave the rational clinician the basis for saving toxicity — and expense — to patients with low risk disease. Hallelujah!
Other exciting concepts
In the domain of advanced disease, we have seen some really exciting new concepts reported. They use all the recently fashionable statistical ploys, but they translate into real potential clinical benefit that can easily be seen even with the old measures. Examples include inhibition of c-MET in cancers of the prostate and bladder, as well as PD-L1 inhibition in several domains, including bladder cancer.
A study by Andrea Apolo, MD, and colleagues, who examined the effect of cabozantinib on immunosuppressive subsets of patients with metastatic urothelial carcinoma, produced three survivors beyond 1 year among 23 heavily pre-treated patients. That’s impressive without statistical mumbo jumbo, and I’m sure Dr. Apolo will test it carefully in structured clinical trials, as she always does.
Similarly, the work of Emmanuel S. Antonarakis, MD, and colleagues from Johns Hopkins Medicine — which focused on the androgen receptor mutation AR-V7 and its strong predictive capability for identifying resistance in prostate cancer, as well as potentially appropriate cost-effective selection of some of the effective new agents — was another highlight.
Let me be quite clear: Not all of the works to which I allude represent level one evidence, but they do reflect well-designed studies (sometimes even as simple as real responses in phase 1), exciting new science-based concepts representing painstaking research, and a preparedness to advance hypotheses and test them before claiming victory without data.
Congratulations to all of these talented colleagues, whose work will actually achieve cure or meaningfully prolong hundreds of thousands of lives, or avoid unnecessary toxicity and/or expense — especially to my friend of more than 30 years, Cora Sternberg, for her tenacity, conviction and ultimate belief in data!
References:
Antonarakis ES. N Engl J Med. 2014;371:1028-1038.
Raghavan D. Clin Cancer Res. 2014;20:3630.
Sternberg CN. Lancet Oncol. 2014;1:76-86.
The following were presented at the ASCO Annual Meeting; May 30-June 3, 2014, Chicago:
Apolo AB. Abstract #4501.
Sweeney C. Abstract #LBA-2.
For more information:
Derek Raghavan, MD, PhD, FACP, FRACP, FASCO, is HemOnc Today’s Chief Medical Editor, Oncology. He also is president of Levine Cancer Institute at Carolinas HealthCare System. He can be reached at derek.raghavan@carolinashealthcare.org.
Disclosure: Raghavan reports no relevant financial disclosures.