Editor’s Note

voyages of discovery

“This is what the Venetians sensed when Marco Polo came back from China — there was this whole cartload of exotic fruits and spices and different cloths and funny animals that no one had ever seen before, and books in different languages. As we look at the biologic agents coming along, novel hormone-based therapies, and new opportunities for chemotherapy, there is a tremendous sense of the horizons expanding. Everybody in ‘Venice’ is running around enthralled by all the different new choices, and they are now sending out their own ‘voyages of discovery’ to see what comes back. This is a taste of what people have been talking about for decades in terms of targeted therapies, and we are entering a golden age for clinical research.”

— Harold Burstein, MD, PhD

Harold Burstein's enthusiasm for discussing the future of targeted systemic therapy is matched by his reluctance to detail current standards of care. Like most clinical researchers immersed in randomized trials that require a flip of the coin to determine treatment, Harold is tough to pin down about his favored interventions in specific practice situations.

However, during our recent interview on the enclosed audio program, we stumbled upon a simple way to separate clinical decisions, using the example of the management of the patient with HER2-positive breast cancer.

Interventions that are standard:

For women with HER2-positive metastatic breast cancer not being considered for endocrine therapy, Dr Burstein — like most breast cancer investigators — considers trastuzumab as a baseline for therapy, with the major question being whether chemotherapy should also be administered.

Interventions that should not be utilized outside of a clinical trial setting:

Citing the widespread accessibility to adjuvant randomized trials, Dr Burstein believes that trastuzumab should not be used in a nonprotocol setting as adjuvant therapy.

Everything else:

Oncologists are constantly challenged to choose between similar treatment options, and their decisions are often based on indirect trial comparisons and clinical experience. Again citing a common HER2 situation, Dr Burstein refers to the encouraging phase II trial data reported by his group at Dana Farber on the combination of trastuzumab and vinorelbine.

While the documented survival advantage of the trastuzumab and paclitaxel combination often leads clinicians to use this regimen as first-line therapy, Dr Burstein believes that either vinorelbine or paclitaxel is a reasonable choice to add to trastuzumab outside of a protocol setting and notes that a current randomized trial will address this key question.

In addition to Dr Burstein's comments on decisions about trastuzumab, the enclosed audio program presents the prespectives of several other research leaders on other key clinical decisions in the "everything else" category including:

The current role of anastrozole as adjuvant therapy:

Dr Jack Cuzick — independent statistician for the ATAC trial — reviews the dilemma facing clinicians with the early, but very promising results, that suggest an advantage for anastrozole compared to tamoxifen.

Combination versus sequential chemotherapy for metastatic disease: Dr William Gradishar reviews the results from a phase II study evaluating capecitabine combined with paclitaxel. Unlike the randomized phase III trial with capecitabine/docetaxel, this new study was designed without a mechanism to document survival advantage. However, Dr Gradishar argues that both combinations are rational clinical choices, particularly in women with life-threatening metastases.

The optimal sequencing of single-agent chemotherapy for metastatic disease:

Dr David Miles reviews provocative follow-up results from the capecitabine/docetaxel trial suggesting that single-agent capecitabine has significant activity when administered after progression on docetaxel. Dr Miles believes that reversing the sequence of these agents may be a reasonable option in clinical practice.

Several months ago, the Breast Cancer Update team conducted a random national telephone survey of 200 oncologists and surgeons to increase our understanding of practice patterns in the community. Presenting scores of controversial clinical scenarios, we obtained a plethora of data, and the initial results were presented in March 2002 at the Miami Breast Cancer Conference.

A full report is currently being compiled and will be included as a special supplement to the next issue of Breast Cancer Update, and a few examples are included in this booklet. The diversity in treatment patterns is very striking and demonstrates the challenge of the "everything else" decisions.

Many other breast cancer research leaders share Dr Burstein's vision of a new era of targeted and more effective therapy, but at the moment, oncologists and patients must make daily, difficult decisions on imperfect interventions with conflicting supporting data.

The Miami Breast Cancer Conference Patterns of Care Survey suggests that there is a spectrum of clinical practice in oncology that narrows considerably whenever new randomized trial results become available. As more "voyages of discovery" lead to clinical research results, we will continue to query investigators about what this means to the patient seeking care.

—Neil Love, MD

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