a change of place

By |September 7th, 2014

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ES

(what follows here at ML will be old posts, rotated occasionally):

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By |September 7th, 2014|Categories: Blogs, from the author, journalism||Comments Off

Palbociclib Appears to Prolong Progression Free Survival in Women with Metastatic Breast Cancer

By |April 7th, 2014

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Yesterday researchers at the annual AACR meeting announced the results of a clinical trial of a new drug with activity in some forms of breast cancer. Palbociclib (PD-0332991), a pill developed by Pfizer, was tested in women with metastatic breast cancer cells with estrogen receptors and lacking Her2. These ER+/Her2- tumors represent the most common breast cancer subtype, which is one reason so many people are eying the results of this relatively small, randomized study.

The phase 2 trial, called PALOMA-1 included 165 post-menopausal women with advanced ER+/Her2 negative disease. The research subjects were assigned to take either Letrazole (Femara, an aromatase inhibitor, a drug that inhibits estrogen synthesis) alone, or Letrazole and also the experimental drug, Palbociclib. The study found a highly significant difference in progression free survival (PFS), the intended endpoint: the mean time until disease progressed was 20.2 months among women who took Palbociclib, as opposed to 10.2 months for those assigned to Letrazole alone. The p-value for the difference between the arms (1-sided) was 0.0004. That’s a powerful  result.

But there was no statistically significant difference in overall survival between the two groups, a fact that was irksome to some observers, particularly in the biotech investment world, and to some who were reminded of the Avastin story and its fall-out. Most of the women lived for approximately 3 years after enrolling, with a trend of a few months favoring the Palbociclib arm. Another problem is that over half the patients were recruited to the study based on biomarker results, having to do with cyclin D1 amplification and/or loss of p16. So it could be the results are more relevant to breast cancer patients who have those particular changes. How those molecular features, enriched in the final study population, relate to Palbociclib’s usefulness in breast cancer and other tumor types warrants more evaluation, for sure.

My feeling is that this may prove to be a useful drug, not just in breast cancer. Any medication which interferes with cell growth by blocking cyclin-dependent kinases (enzymes) called CDK-4 and -6 could be useful in quite a few malignancies. The main side effect was suppression of the bone marrow (low blood cells). Some questions I’d like to ask the researchers, and which I hope they’ll address in the Phase III study, is if certain types of mets (e.g. lung vs. bone) or certain molecular subtypes are more tempered by this drug.

As for 10 months of PFS – if it pans out in a formal, published work, that’s valuable. Imagine that you’re 55 years old and living with metastatic breast cancer. A drug that is likely to delay, by most of 2 years, your tumor’s expansion into the lungs (causing shortness of breath), or bones (causing fractures and pain) or liver, and elsewhere can be worth a lot. It’s about the quality of life, whether or not it’s extended.

One final concern is that this study wasn’t blinded, so the doctors’ assessment of how the patients were doing, and the patients’ assessment of how they were feeling,  may have been influenced by their knowing which arm they were on. Also, because this new drug is a pill, some insurance may not cover it – a policy issue that applies to many new cancer drugs.

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JAMA Review on Mammography Points to the Need for Better Ways to Advise Women and Detect Breast Cancer

By |April 2nd, 2014

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It’s hard to argue with the findings and conclusions of a new paper in JAMA put forth by Drs. Lydia Pace and Nancy Keating, both physicians with public health degrees and appointments at Harvard-affiliated hospitals. The article, published on April 2, has generated a predictable round of headlines along the lines of “Large Study Finds Little Benefit in Mammography.”

You might, while reading or hearing about this news, wonder about the value of yet another study on breast cancer screening. And you might, if you are following this blog, wonder why I remain convinced that mammography – when done right – has the potential to save many women’s lives and, what’s more, to spare even more from the physical, financial and emotional toll of prolonged treatment for advanced-stage disease.

Why I still think that breast cancer screening is a good idea for most middle-aged women (selected, from a longer list):

1. Several valid studies, most notably that from Sweden, have shown a significant survival benefit of breast cancer screening over the long term. These findings, which demonstrated a benefit to women screened in their forties, received little attention in the news.

2. Mammography is not all the same. It’s not a simple, black-and-white or numeric readout. The “result” depends a lot on the radiologist who interprets the images. Some radiologists, by their training and expertise, deliver lower false positive rates and higher true positive (malignant) “pickup” rates. To say that mammography doesn’t work, based on studies over a population, discounts the potential (and likely) benefit of having the procedure done by experts.

3. Pathology methods have improved over the past three decades. Some doctors, including epidemiologists and PCPs, may not be aware of new tools for evaluating tumors that lessen the risk of over-treating early-stage and indolent tumors.

4. Longer survival is not the only benefit of mammography. Late detection involves risks, and costs. “Screening neglect,” as some researchers call it, adds intensity to needed treatment when patients first seek care for advanced disease. This was the focus of a recent paper in the American Journal of Roentgenology that got little press except for the Cleveland Plains Dealer. The investigators in that careful but retrospective analysis found that among women in their forties, breast cancers detected in routine mammograms were significantly smaller than those detected in women who waited until they felt a lump or had symptoms. That finding was no surprise. But what mattered is that the difference in size of invasive breast cancers found – between screened and unscreened women – translated to less chemotherapy for those screened. The point: finding breast cancer early can reduce the need for toxic and costly treatment.

In reading the new JAMA paper, “A Systematic Assessment…” it seems like the authors are giving a well-prepared talk. Essentially it’s a review of reviews on mammography. Yes, it’s that “meta.” They examined the literature on mammography, going back to 1960 – but with an appropriate emphasis on more recent studies, to address 4 (huge, complex) questions: 1) what is the benefit of mammography screening, and how does it vary by patient age and risk?; 2) what are the harms of mammography screening?; 3) what is known about personalizing screening recommendations?  4) how can patients be supported to make more informed decisions about screening?

This is an ambitious set of questions, to say the least. The tables provided, which are for the most part inconclusive, draw heavily on findings that vary in the era of data collected, methods of analysis, and reasonableness of authors’ assumptions, i.e. validity.

But there is no news on mammography here, except that these two thoughtful investigators carefully reviewed the literature. There are no original data in this ambitious analysis, i.e. there is no new information about mammography’s effectiveness, the false positive rate, the harms of screening, overdiagnosis, etc.

Unfortunately the article, at a glance, may add to the growing perception among journalists, primary care physicians who may not read below the paper’s title, and others – including many ordinary women – that mammography’s effectiveness has been, again, disproved.  And so if journalists cover this “story,” as they have and will, our collective memory will incorrectly recall another negative finding, which this is not.

The authors’ main conclusions are that decision aides may be helpful, and that developing better ways of screening for breast cancer would be even better than that. I agree.

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