Email from the Editor

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A week from tomorrow, the NSABP’s Dr Alexander Paterson will face the San Antonio multitudes and add another important and perhaps punctuating chapter to an oncologic saga that began 10 SABCSs ago when Dr Trevor Powles revealed the results of the first major randomized trial demonstrating the potential anticancer benefits of adjuvant bisphosphonates. Since then, the story has been a roller-coaster ride, which peaked at ASCO 2008 when Dr Michael Gnant’s plenary presentation of the Austrian ABCSG-12 trial suggested an important benefit of zoledronic acid (ZDA). However, last year at San Antonio Dr Robert Coleman crushed the bone enthusiasts with the almost flat-out negative results of the AZURE trial evaluating ZDA versus placebo.

As expressed by Dr Martine Piccart-Gebhart in a 3-minute video clip from our June CME symposium, although you can make an argument to offer ZDA to women who fit the Austrian profile (premenopausal patients with luminal A tumors receiving only endocrine treatment), such patients who do not receive chemotherapy are rarely found in US practice, and the NCCN breast cancer committee chair Dr Bob Carlson notes that the guidelines “remain silent” on this issue, which I think means the evidence is conflicting and what to do is unclear.

Dyed-in-the-wool bone optimists have been looking to NSABP-B-34 to potentially save the bisphosphonate day, and although there’s no way Dr Norm Wolmark or any of the NSABP investigators will prematurely spill the beans about the results, the odds seem to be stacked against this trial for a number of reasons. Perhaps most significantly, clodronate is about 10,000 times less potent than ZDA and in the landmark MRC IX trial comparing these drugs head to head in patients with multiple myeloma, ZDA resulted not only in fewer bone-related events but also in fewer deaths. It is worth mentioning that Dr Powles’ previously mentioned trial was with clodronate, so who knows what will happen?

Regardless of what B-34 shows, the bone candle will continue burning, even if it is ever so faintly, with Dr Julie Gralow’s SWOG-S0307 trial comparing clodronate to ibandronate to ZDA and the so-called D-CARE trial evaluating the RANK ligand inhibitor denosumab as adjuvant therapy for patients with node-positive tumors or other higher-risk factors. This study in particular may be testing a better agent with perhaps better eligibility criteria, correcting the problem with event numbers in B-34 that delayed the data maturation.

Another San Antonio paper I can’t wait to hear is being presented by ECOG’s Dr Lawrence Solin and will detail a retrospective/prospective analysis of a quantitative RT-PCR assay in patients with DCIS that will complement Oncotype DX^® in invasive disease. The data set was derived from tumor tissue from patients s/p lumpectomy for Grade I to II DCIS in ECOG-E5194 who were randomly assigned to the no-treatment arm in this study evaluating the addition of radiation therapy. Although this much-awaited abstract, like all abstracts for San Antonio, is not yet posted (frustrating!), the analysis is purported to identify a biologic subtype with a very low risk of invasive or noninvasive local recurrence.

If these results pan out, not only will 57,000 women a year in the US alone be better supported in their decision-making, but we may look back at this as the moment DCIS joined the biology-driven world that invasive disease entered at San Antonio 2004 when Dr Soon Paik presented the first Oncotype DX data. This will be a welcome change from the “My margins are bigger than yours” debates that currently dominate DCIS discussions at surgical meetings. (Click here for a 3-minute video with our faculty’s comments on another key surgical paper, last year’s landmark ACOSOG Z-0011 on axillary dissection.)

Our faculty poll demonstrates that Oncotype DX is currently used selectively in node-positive disease (click here for 4 minutes of related comments) and for node-negative tumors the same chemo regimen is used in patients with high or intermediate Recurrence Scores^®.

If the data sets mentioned in the 3 emails that make up this miniseries haven’t done enough to whet your appetite for what will come in San Antonio, worry not, as there will be more than 1,000 presentations across the conference’s 3 days. How and if these change current practice remains to be seen, but check out the attached matrices to get a good sense of where we are today for a variety of other early disease treatment scenarios.

Next up on this email journey, an important neoplasm that is struggling to enter the novel agent world: Hepatocellular cancer.

Neil Love, MD
Research To Practice
Miami, Florida