Three Reasons to Celebrate the Supreme Court’s Decision on Obamacare

I’m thrilled about today’s SCOTUS decision. The Supreme Court upheld the gist of the Affordable Care Act (ACA). Am I surprised? Yes, like pretty much everyone – I didn’t anticipate Chief Justice Roberts’ clever argument about the individual mandate.

What I see in this is first, a win for patients, who now are more likely to get health care if and when they need it – preventive and otherwise. L’Chaim!

Second, it’s a win for the Obama administration and the Democrats. And although I went to journalism school at Columbia University and was told that “real journalists don’t share their opinions,” I do: I’m a registered, reliable, primary-voting Democrat. The ACA is, so far, President Obama’s signature achievement. This SCOTUS decision supports the President’s goal of simultaneously reining in health care costs and expanding coverage to all. It raises the likelihood of President Obama’s re-election. Cheers!

Finally, and at a deeper level, the decision reflects the power of one man’s thoughtfulness to change the outcome of a seemingly bleak situation. (This can happen in oncology and other kinds of medicine, when most of the doctors or specialists on a case throw up their hands or say “it’s impossible because of blah, blah, blah,” and they might refer to some old published studies on old drugs, or something like that.) What Chief Justice Roberts did was think out-of-the box, carefully and within a legal framework. Like a good, smart doctor, morally grounded and, perhaps, influenced by compassion (hard to tell), the Chief Justice figured out a legally acceptable way for his court to do the right thing. By his wisdom, he will have saved more than a few lives. Bravo!

Related Posts:

Reading Between the Lines, and Learning from an Epidemiologist

Early on in Between the Lines, a breezy new book on medical statistics by Dr. Marya Zilberberg, the author encourages her readers to “write, underline, highlight, dog-ear and leave sticky notes.” I did just that. Well, with one exception; I didn’t use a highlighter. That’s partially due to my fear of chemicals, but mainly because we had none in my home.

I enjoyed reading this book, perhaps more than I’d anticipated. Maybe that’s because I find the subject of analyzing quantitative data, in itself, dull. But this proves an easy read: it’s short and not boring. The author avoids minutia. Although I’m wary of simplified approaches – because as she points out, the devil is often in the details of any study – this tact serves the reader who might otherwise drop off this topic. Her style is informal. The examples she chooses to illustrate points on medical studies are relevant to what you might find in a current journal or newspaper this morning.

Over the past year or two, I have gotten to know Dr. Zilberberg, just a bit, as a blogging colleague and on-line associate. This book gave me the chance to understand her perspective. Now, I can better “see” where she’s coming from.

There’s a lot anyone with an early high school math background, or a much higher level of education, might take away from this work. For doctors who’ve attended four-year med schools and, of course, know their stats well (I’m joking, TBC*), this book provides an eminently readable review of basic concepts – sensitivity, specificity, types of evidence, types of trials, Type II errors, etc. For those, perhaps pharmacy student, journalists and others, looking for an accessible source of information on terms like “accuracy” or HTE (heterogeneous treatment effect), Between the Lines will fill you in.

The work reads as a skinny, statistical guidebook with commentary. It includes a few handy tables – on false positives and false negatives (Chapter 3), types of medical studies (Chapter 14), and relative risk (Chapter 19). There’s considered discussion of bias, sources of bias, hypothesis testing and observational studies. In the third chapter the author uses lung cancer screening scenarios to effectively explain terms like accuracy, sensitivity and specificity in diagnostic testing, and the concept of positive predictive value.

Though short, this is a thoughtful, non-trivial work with insights. In a segment on hierarchies of evidence, for example, the author admits “affection for observational data.” This runs counter to some epidemiologists’ views. But Zilberberg defends it, based on the value of observational data in describing some disease frequencies, exposures, and long-term studies of populations. In the same chapter, she emphasizes knowing – and stating – the limits of knowledge (p. 37): “…I do think we (and the press) do a disservice to patients, and to ourselves, and to the science if we are not upfront about just how uncertain much of what we think we know is…”

Mammography is, not surprisingly, one of few areas about which I’d take issue with some of the author’s statements. For purposes of this post and mini-review, I’ll leave it at that, because I think this is a helpful book overall and in many particulars.

Dr. Zilberberg cites a range of other sources on statistics, medical studies and epistemology. One of my favorite quotes appears early on, from the author directly. She considers the current, “layered” system of disseminating medical information through translators, who would be mainly physicians, to patients, and journalists, to the public. She writes: “I believe that every educated person must at the very least understand how these interpreters of medical knowledge examine, or should examine, it to arrive at the conclusions.”

This book sets the stage for richer, future discussions of clinical trials, cancer screening, evidence-based medicine, informed consent and more. It’s a contribution that can help move these dialogues forward. I look ahead to a continued, lasting and valuable conversation.

 —

*TBC = to be clear

Related Posts:

How Much Do You Want Your Doctors To Say About Risks of Treatment?

When I was diagnosed with breast cancer, I was working as a board-certified oncologist. The initial decisions most patients face – which doctor to see, what kind of doctor to see, and at which medical center to see them – were basically non-decisions. I knew, within an instant of my diagnosis, who I’d ask to be my oncologist, surgeon and plastic surgeon. Those choices were straightforward, because I knew what those physicians were like in terms of how they cared for patients, their knowledge and other aspects of their practices and personalities.

The harder decisions were what treatment to take, or not, for my early-stage breast cancer. I was perhaps the most informed cancer patient who could walk into an oncologist’s office. I was familiar with the different regimens. I knew that adjuvant chemotherapy would, roughly and over the long haul, reduce my odds of recurrence by a third. I was aware that, if I opted for a lumpectomy, radiation treatment would reduce the local recurrence rate but was unlikely to affect my long-term survival. I understood that dose-intense regimens were more likely to make me sick and more likely to cause problems down the road.

And yes, in the back of my head I knew that chemotherapy can cause another cancer. Did I think about that possibility? The best answer is, probably, not so much. I was coping with the present.

But that knowledge did influence the decision I made to take a relatively “light” dose of chemotherapy. I was lucky, also, in that I understood my pathology. My tumor, at 1.5 cm, with a negative sentinel node and generous expression of hormone receptors, was a good-prognosis tumor. I was 42 years old, and wanted to live for a few more decades if I survived my spine surgery (another story). I chose the minimal amount of chemo that had been shown in clinical trials to reduce the odds of recurrence.

Last week, I wrote a piece for the Atlantic on how doctors and patients talk about the risks of chemotherapy, or not, and whether patients listen or necessarily want to listen. The reason I put it out there is because I’ve seen doctors shy away from this part of the conversation about cancer treatment. I’m a firm believer in informed consent, and in patients’ access to as much information as they choose to have. If you get chemotherapy, you have the right to know about these risks, and to ask your doctor about them.

I’ve been there with patients who’ve said: “please, don’t tell me this. I can’t deal with it.” Some might even consider it cruel to tell patients with a serious, urgent and treatment-needing condition details of all the possible side effects. Many ask, “what would you do, doctor, if it were someone in your family?” And if they like and respect you, they go with your recommendation.

This kind of paternalism, when a doctor assesses the risks and benefits, and spares the patient’s “knowing” seems anachronistic. But it may, still, be what many people are looking for when and if they get a serious illness. Not everyone wants a “tell me everything” kind of physician. What do you think?

Related Posts:

This Week’s Triple, Tough Dose of Real Stories on Women with Cancer

Dear Readers,

It’s been a tough week on the breast cancer front.

Many in the community first learned that Ellen Moskowitz, a former leader at the Metastatic Breast Cancer Network (MBCN), died. Ellen was a funny, articulate woman who lived with MBC. When I interviewed her for an article on the value of a day designated to awareness about metastatic disease, she kept me laughing.

Robin Roberts, a co-host of Good Morning America who was treated for breast cancer less than 5 years ago, announced that she’ll be getting a bone marrow transplant for MDS. The blood condition is, in some cases, a complication of chemotherapy. I wrote a piece about this for the Atlantic Health. This unfortunate news reminds us an aspect of cancer treatment some of us would rather put out of our heads. The main message – which I hope came through editing – is that all cancer patients should take careful notes on their planned treatments and ask their doctors about the long-term consequences of therapy. Not all chemo is the same; the risks vary among regimens and doses. The reality is that some of us – patients and doctors – prefer not to think about late, long-term, possible effects of treatment, like secondary tumors, when there’s a life-threatening condition in hand. This doesn’t mean chemo isn’t the right choice. Often it is, but it should be weighed out, carefully.

Finally, we learned that Dr. Susan Love, a breast surgeon and professor at UCLA, and leader of an Army of Women, has leukemia. Dr. Susan Love’s Breast Book is a reference my friends and patients turned to in the 1990s, before the Internet was so loaded with cancer info, and many still do. She has, through that book and through her Foundation, besides through her work as a surgeon, helped an army of women to heal, and more.

My thoughts are with each of these remarkable women, and their loved ones, now.

ES

Related Posts:

FDA Approves Pertuzumab for Advanced, Her2+ Breast Cancer

We’re on a roll for new treatments of the Her2+ form of breast cancer. On Friday the FDA approved Pertuzumab, a monoclonal antibody, for advanced cases. As indicated, the drug would be given along with another monoclonal antibody, trastuzumab (Herceptin) and a chemotherapy, docetaxel (Taxotere) to patients with advanced breast tumors with high levels of Her2.

The new treatment’s brand name is Perjeta. Like Herceptin, this reagent works by attaching to the Her2 receptor on a cancer cell’s surface. But it differs by binding a distinct part of the molecule; its mechanism of action is said to complement that of Herceptin.  You might recall that HER protein family members are complex signaling molecules that span cell membranes. Her1 is the Epidermal Growth Factor Receptor; it’s turned on when bound by its partner, or molecular ligand, Epidermal Growth Factor(EGF). The others are Her2, -3 and -4.

EGFR (Her1) signaling, Wiki-Books image

The science behind drugs that interfere with Her2 receptors and signaling is nicely summarized in a recent, open-access Nature Reviews Clinical Oncology article. Herceptin binds a particular segment of Her2 on the outside of the cell; this leads to failed signaling on the inside, including cell division signals, and causes cell death by several mechanisms. Pertuzumab binds a distinct segment of Her2 in such a way that it can’t form a complex with the related Her3 molecule; this interaction is needed for Her2 to stimulate cell growth.

The FDA’s approval rests largely on results of the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) study, published earlier this year in the NEJM. In that Phase III study, just over 800 patients were randomly assigned to receive a standard regiment – Herceptin in combination with Taxotere plus a placebo infusion, or the Herceptin-Taxotere combination plus Pertuzumab.

The patients who received Pertuzumab did better in terms of Progression Free Survival (PFS, 18.5 months vs. 12.4 months; this difference holds strong statistical merit). There is a trend, also, in terms of Overall Survival: at a median follow-up point of 19.3 months, there were more deaths in the placebo group. But a statistically significant difference was not reached. Toxicity was reported as “generally similar” in the two groups, but there was more diarrhea, dry skin and rashes among those who got Pertuzumab (Table 3). Heart problems, a known toxicity of the Herceptin-Taxotere regimen, were slightly less common with Pertuzumab. Hair loss, presumably from the chemotherapy part of the regimen, was common in both groups.

One curious thing I noticed, in re-reading the January report, is that although the median age for both patient groups was 54 years, the control patients ranged from 27 – 89 in age; those who got Pertuzumab ranged from 22 – 82 years. Although the younger “shift” of Pertuzumab-receiving patients relative to the controls is unlikely to affect the PFS, it’s odd to include an 89 year old patient on an experimental protocol involving infusions of two monoclonal antibodies along with chemo.

This is a super-costly regimen. Like Herceptin, and like the experimental compound antibody, DM1, about which I wrote last week, Perjeta is manufactured by Genentech. As detailed by Andrew Pollack in the NY Times: the wholesale price for Perjeta will be $5,900 per month for a typical woman; Herceptin costs $4,500 per month. So we’re talking about a treatment in which the monoclonal antibodies alone cost over $10K per month. “A typical 18-month course of treatment would be more than $187,000,” he indicated. But if you add on the costs of the Taxotere, drugs like Benadryl and Decadron to minimize allergic reactions, anti-nausea meds, charges for the infusion and monitoring…It’ll be a lot more than that.

As the FDA notes in its press release, production of Perjeta is currently limited due to a technical issue at the Genentech manufacturing plant. Meanwhile, investigators, doctors and patients will have to sort out the relative value of this drug, on top of the others – including pills – for Her2+ disease.

My opinion is not quite formed on this new antibody. The FDA’s decision was based on results from one trial of 808 patients, half of whom didn’t get the experimental drug. Accrual began in 2008; its broad clinical effects, and long-term toxicities, can’t be established yet. It may be, ten years from now, that Perjeta will be used routinely in patients with other, Her2+ kinds of cancer. Or it may be a toxic bust.  How (and if) we’ll test and compare different doses of Perjeta and potential combinations with other drugs, small pills and traditional chemotherapies – which are many – is not clear. You could, for example, combine one or both of the antibodies with a drug like Lapatinib (Tykerb), that inhibits Her2-triggered growth signals inside the cell.

The problem is that oncologists, and facilities including academic centers where revenue is generated by giving drugs by infusion, now have a huge financial incentive to give the Herceptin-Perjeta-Taxotere regimen. This regimen is approved for first-line treatment of metastatic, Her2+ breast cancer; you don’t have to have “failed” another regimen, as was required for the EMILIA trial. As I understand this approval, an oncologist seeing a woman with recurrent or metastatic Her2+ breast cancer could, immediately, prescribe the 3-drug combination.

It’s impressive that the CLEOPATRA folks included an 89 year old patient in the study. But at some point, you have to wonder where we might draw lines. I’ve no answers on that.

All for now, maybe for the week,

ES

Related Posts:

On Sheryl Crow’s Report that She Has a Meningioma, and Singing Loud

This morning CNN fed a headline: Sheryl Crow: ‘Brain Tumor is a Bump in the Road.’ This concerned me, not only because I’m a huge fan, but because in 2006, she began treatment for breast cancer at age 43. “Singer-songwriter Sheryl Crow says she has a brain tumor,” says the first line of the CNN story. I was concerned. It seemed liked she’d been getting a little bit closer…to feeling fine.

Fortunately, the LATimes and People magazine got Crow’s story right. Their headlines, and text, emphasize the benign nature of Crow’s newly-diagnosed condition, a meningioma. Most meningiomas are benign, local expansions of the cells that line the brain and spinal cord. These growths occasionally cause neurological symptoms. Some patients have surgery to relieve or avoid complications of these non-malignant growths, but many don’t need intervention. When I was an oncology fellow I learned that meningiomas were relatively frequent in women with breast cancer, but that association turned out to be untrue. The “lesson” back then was that if a scan shows a brain mass in a woman with breast cancer, you shouldn’t assume it’s a brain met, because meningiomas were not rare in women with a history of breast cancer. According to the NCI website today, meningiomas are more common in women than in men.

Singing ‘Rock and Roll,” on top of a piano

Cancer scares aside – I’m glad that Sheryl Crow’s brain mass is benign, and that she can keep on singing if she chooses. I’ve seen her twice in concert, and she’s amazing. I have several favorite songs of hers, but the most memorable moment from a performance I’ve seen was when she got up on top of the piano at Radio City and sang Led Zeppelin’s Rock and Roll. I wish I could do that! She’s a powerful woman, for sure.

—-


Related Posts:

Sad News, from the Metastatic Breast Cancer Network

Dear Readers,

I was saddened today to learn of the death of Suzanne Herbert. Last October, I met Suzanne at a conference. She seemed familiar; that was because I’d read about her life with metastatic breast cancer (MBC) a few months back in the New York Times. Like some women I’ve known w/ MBC, Suzanne didn’t appear sick. At least not then. She seemed positive, and thoughtful. Energetic, even.

According to the Metastatic Breast Cancer Network, Suzanne lived with metastatic disease for over 7 years. She died last week at age 47.

– ES

Related Posts:

EMILIA Trial: T-DM1 Appears Helpful in Women with Her2+ Metastatic Breast Cancer

This weekend the American Society of Clinical Oncology (ASCO), to which I belong, is holding its annual meeting in Chicago. Some of the biggest buzz has to do with a new breast cancer drug called T-DM1. ASCO just lifted embargo of the relevant abstract.

The new agent is a hybrid of an old monoclonal antibody, Herceptin, that’s chemically attached to DM1, a traditional kind of chemotherapy. The chemo part, DM1 – also known as emtansine – is manufactured by ImmunoGen. It’s derived from maytansine, a compound that binds tubulin, a protein critical for microtubule formation in dividing cells. According to the NCI website, this chemical, which has antibiotic properties, was extracted from an Ethiopian plant, Maytenus serrata.

T-DM1 was designed by linking the DM1 compound to the trastuzumab (Herceptin) antibody. Trastuzumab is old news in breast cancer. It binds a signaling molecule, Her2, that’s expressed at high levels in approximately 1 in 5 breast tumors. The FDA approved Herceptin for use in patients with metastatic, Her2+ breast cancer in 1998 and, for some women with localized, lymph node positive disease, in 2006. In this new, hybrid drug, the antibody works like a tagged, toxic messenger. In effect, the antibody delivers and inserts the chemo into the malignant cell, where it causes cell death.

The new data, from the Genentech-sponsored EMILIA trial, were presented today:

The Phase III study evaluated 991 women with metastatic breast cancer. All participants had tumors with high levels of Her2 (confirmed in a central pathology lab, for the trial). All had disease that progressed despite treatment with Herceptin and, in most cases, other drugs too. After randomization, 978 women received either of two treatments: the experimental agent, T-DM1, every 3 weeks, by intravenous infusion, or a combination of two pills, “XL” – Xeloda (capecitabine) and Tykerb (lapatinib). Median follow-up was just over 1 year – not bad for a study of MBC, but not great, either.

The big news is this: Among the patients who got the experimental drug, T-DM1, the median time until disease progressed was 9.6 month; for those who took the XL pill combination, it was 6.4 months. This different was statistically significant. Although a difference of 3 months may not sound like much – and isn’t – each regimen in the study held the women’s disease in check for over half a year.

It’s striking that T-DM1 was used as a single agent. Most chemotherapy drugs, like those for HIV, work best in combination; it could be that we’ll see more powerful results in a few years, once we learn how to optimally combine drugs for women with Her2+ breast cancer.

As far as overall survival, the initial results seem quite favorable. Among women on the study for 2 years, 65 percent were alive who received T-DM1; among those taking the XL regimen, 47 percent were alive at 2 years. (The statistical details for this comparison are not available; evidently it was of weak significance.) The problem is – if only a few patients were analyzed “so far out” on the survival curves, the difference observed between the two study arms might be random. Still, and independently of the comparison, survival of 65 percent at 2 years in this patient group is (sadly) impressive, especially if it comes by a single agent with comparatively few side effects.

The main T-DM1 toxicities were low platelets and abnormal liver function, which were, reportedly, reversible. The XL combination caused more toxicity, overall, including diarrhea, hand-foot syndrome and nausea.  A much greater fraction of women on the XL arm (53 and 27 percent, respectively for Xeloda and lapatinib) needed dose reductions, as compared to the T-DM1 (16 percent had dose reductions due to toxicity). Evidently hair loss isn’t an issue for women who get T-DM1, which is nice.

My main, initial concerns are two:

First, the study, though randomized, is not “blinded,” and can’t be.  It’s impossible for women who are getting an intravenous drug, and their doctors, not to know that they’re not on the pill study arm. Although there were independent evaluators of progressive disease, which is a far more subjective measurement than overall survival, progression free survival can be influenced by the doctors’ and patients’ knowing they’re getting the T-DM1. That said, the initial, observed difference in overall survival – a clear, objective measurement – is impressive.

If these trial results, published in abstract form, pan out, and the quality of patients’ lives is maintained, that’d be helpful to as many as 1 in 5 women with MBC. It is plausible that an antibody like Herceptin that targets the tumor cells could, in fact, “deliver” the chemo effectively into the cancer cells with relatively low toxicity. And if the women are feeling better, which is hard to know from an abstract, great.

My second concern is how this drug will mesh with others now available and in the pipeline for patients with Her2+ disease. In a December, 2010 editorial in the JCO, two clinical investigators wrote: “the unique aspect of T-DM1 is clearly its high clinical activity by itself, without the need of concomitant additional systemic chemotherapy.” They’re right. The question – as considered by those authors – is how T-DMI will be used in the context of expanding treatment options for women with Her2+ breast cancer. This is an expensive (price not yet known) monoclonal antibody-conjugate that’s necessarily given by infusion. Testing this drug against all the other current and up-and-coming alternatives, in varying combinations and doses, will be tricky. The trials alone will cost big bucks, besides toxicity and women’s lives.

These EMILIA results are promising for some women with MBC and, possibly, patients with other cancer forms in which Her2 is expressed. Unfortunately, it’s unlikely to help those women with breast cancer whose tumors that lack Her2+.

I’ll write soon about this new class of oncology drugs – antibodies conjugated to chemotherapies, as a group.

All for now,

ES

Related Posts:

newsletter software
Get Adobe Flash player