More on HIV and Poverty in the U.S.

By Jessica Wapner
Posted: May 4, 2012

Many years ago, some friends of mine in Israel dug a hole. I don’t remember now what they were searching for, but they thought there was something a ways down, so they dug. It took a while, and in the end they had a very deep hole. But, what they had been looking for turned out to not be there. So now they had a hole with nothing to show for it. Someone came up with a very surprising way to make use of the hole. Again, sorry, I don’t remember the details, but it was something wonderful. And the wisdom of the moment was: Why waste a good hole?

My last post was a brief survey of the landscape connecting HIV and poverty, with a selection of slides from a talk I was about to give at the American Association for the History of Medicine meeting. Having gathered together the information, I thought I’d post the remainder, because why waste a good slide.

You know how there are some topics which, when you come across them, you think: why aren’t we talking about this every day? How can the world just kind of keep going on when this problem exists? How is it possible that someone is spending more than $100 million dollars to keep The Scream in a private collection, or to ensure someone’s election into office, when there are children being born into situations that put them at high risk for diseases that they’ll spend their entire lives coping with, or from which they will die way too young? It’s not that I think the people spending that money should be directing it elsewhere; it’s that we live in a world where economy trumps humanity at every turn. I know, I know, this is a blog about science, not social justice, but sometimes a topic arises where the two can’t be kept separate.

There are a zillion issues like this, too many to name, or almost think about. Admittedly, delving into the many health disparities connected with poverty isn’t something I do every day. But having gone there, I’m finding it hard to leave.

Anyway. Onto the slides.

In the last post, I included some stills from this moving portrait of how HIV has shifted over the past two decades. Here are some more statistics about that:

The AIDSVu project, conducted by Emory University, found that nearly all U.S. counties with high rates of HIV and infection are located in the south. To be more exact, of the 175 counties in the top 20% for HIV and poverty, all but six are in the south.

According to the 2010 CDC report, Communities in Crisis, heterosexuals living below the poverty line in U.S. cities are five times as likely as the general population to be HIV-positive, regardless of race of ethnicity. Among people living in the same neighborhood but above the poverty line, the likelihood of being HIV positive was 2.5 times higher than among the general U.S. population.

Here is another way to consider the overlap of poverty and race/ethnicity:

So, the CDC is saying that the main connection between HIV and race/ethnicity is through the conduit of poverty. When you look at the entire U.S., HIV rates are staggeringly higher among blacks. But when you zero in on poverty, the racial/ethnic disparities almost disappear. Similarly, sexual orientation becomes less of an issue. In that CDC study, which was based on 9,000 people in 23 cities, 2.1% of heterosexuals living in high-poverty urban areas were HIV positive. Note that the definition of an epidemic is when the rate of a disease in a given location exceeds 1%.

The last post also mentioned that HIV is one of many diseases of poverty. Of course this is looking only at the U.S.—when you extend the view to the entire world, the connection becomes only more harrowing, as shown very starkly in this WHO report, Disease of Poverty and the 10-90 gap. (PDF) (10-90, as in: 10% of the world’s population get 90% of the healthcare.)

In the U.S., diabetes is another disease connected with poverty. Here is a slide that was included in the last post showing the prevalence of diabetes in the U.S.:

The map above covers all regions of the country where income spans from $19K/year to $112K/year.

Now here is a version of the map filtered to include areas where the average income ranges from $19K/year to $34K/year:

The two maps reveal the areas where lower-income plus diabetes incidence are most concentrated.

A major issue inside this territory is that of education. Educational disparities are also linked to disease. Having not really done much research to better understand, in a clear and factual way, why poverty and education and disease seem to be linked together, I’m not going to assume any explanation. But here are some small glimpses that show the link exists.

I hope you can see this slide clearly enough. It shows the potential number of deaths from cancer that could have been prevented by eliminating educational and/or racial disparities among people ages 25–64 in 2007:

The light blue in the charts above, which you’ll note encompasses more than half the pie for African American men, shows the deaths that supposedly could have been avoided.

Among the 10 states with the lowest high school graduation rates (less than 65%), seven are in the southern U.S. Whether that bears any direct relevance to HIV rates in those states, I don’t know.

Here’s some more interesting information, now focused on sex education. There are a lot of states that don’t mandate sex education or HIV education.

For a better view of that, a PDF is available here, with a lot more information about where American teenagers get information about sex. Several states in the U.S. allow abstinence-only sex education.

Here is more about the link between education and health, from the National Poverty Center (PDF). 

Finally, some more information about healthcare among people living with HIV.

The CDC recommends HIV screening as part of routine medical care. Yet in many states, Medicaid does not cover routine HIV screening. According to the CDC, “States in the South were least likely to cover routine HIV screening (4 of 16).” This map shows where such screening is (dark blue) and isn’t (light blue) covered:

Finally, a look at poverty rates across the country. According to the U.S. Census Bureau, rates are rising faster in the southern U.S. than in other regions. From 2009 to 2010, there was a 1.2% rise in poverty in the South, about double the rise seen in the Northeast, Midwest, or West. The share of the U.S. population earning below half of the federal poverty line has risen to 6.7%, a record high.

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Category: Healthcare disparities, HIV | Tagged , , , , , , , , , | 2 Comments

HIV and Poverty: A Slide Show

By Jessica Wapner
Posted: April 27, 2012

This Saturday, April 28th, I’ll be joining documentary filmmaker Lisa Biagiotti and Stephen Inrig, a professor at UT Southwestern Medical Center, on a panel session at the annual meeting of the American Association for the History of Medicine. Our talk will focus on HIV in the Southern U.S., with my portion focusing in particular on the connection between HIV and poverty in the region.

In creating some slides to show during the talk, I was struck yet again by the starkness of this connection, and of the deeply engrained link between socioeconomic status and health. Because I know many people feel likewise alarmed and simultaneously glad to be aware and reminded about these connections, here is an extract of the slide set, with some explanations here and there.

The U.S. Census Bureau includes the following states/regions in its definition of the southern U.S.: Washington D.C., plus Alaska, Arkansas, Delaware, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Texas, Tennessee, Virginia, West Virginia.

Here’s a look at the distribution of wealth in the U.S. According to the U.S. Census Bureau, of the 12 states with >30% of its population living in poverty, 12 are in the South:

Viewed from another angle, the five states with the lowest personal income per capita in 2007 (which I realize is several years ago now) are all in the southern U.S:

When HIV was first found in the United States in 1981, it was concentrated mainly in coastal cities, and did not turn up in any particular population in terms of race or economic status:

This moving image created by Scientific American, in conjunction with an article I wrote for that magazine about HIV in the South (Poor Man’s Burden, with much credit to editor Christine Gorman), chronicles the shift in geography that HIV has undergone in the United States since 1981. Here is the 2009 view:

Scroll back and forth between those two images to see how the orange circles have changed location.

Over time, HIV has come to be concentrated in areas stricken by poverty. To be sure, there are other factors that have contributed to the rise in HIV in the southern U.S.—social stigmas, for example—but economics is a major issue, and one that is tightly linked to race. Here are some statistics about HIV in the southern U.S.:

Here is a particularly stark view, showing HIV levels in several countries:

And let’s remember, the U.S. is the country that spends the most on healthcare in the entire world.

Here’s one more look at the link between HIV and income levels. Note the quote from the CDC’s report, “Communities in Crisis,” stating the inverse link between poverty and annual household income.

The connection with race is also clear, as in this chart and the statistics noted below:

In case it’s hard to read, here are some statistics:
• More than half of all poor and black households are in the south
• Blacks are 13% of the U.S. population and 51% of people living with HIV/AIDS
• The estimated lifetime risk of HIV is:
- 1 in 16 for black males
- 1 in 30 for black females
- 1 in 104 for white males
- 1 in 588 for white females

Of course, HIV isn’t the only illness linked to poverty. Diseases of poverty also include heart disease, diabetes, obesity, and some types of cancer (as former director of the NCI Samuel Broder once said, “poverty is a carcinogen.”). Here’s a look at the distribution of diabetes in the United States:

There are numerous reasons why poverty is linked to disease, and HIV in particular. Poverty is associated with inadequate education, limited healthcare, and inadequate career opportunities. The limit on career opportunities can prevent people from obtaining the independence needed to resist risky behavior. Poverty is also associated with higher rates of incarceration, which has a dramatic impact on the surrounding community. The quote in the slide below says so much:

Regarding the access to healthcare, poverty restricts it. In many states, Medicaid eligibility sets federal poverty level limits that leave many people ineligible, but yet unable to afford private insurance. Here is a look at the percentages of uninsured people under 65 and children under 18 in the United States in 2008:

Another problem with Medicaid is that routine HIV screening is not covered in many areas. The CDC reports that only 4 of 16 states in the South routinely cover HIV screening, even though this approach is recommended, especially considering that among the 1.2 million people currently living with HIV/AIDS, about 1 in 5 don’t know they are infected. Here is a look at where routine HIV screening is and isn’t covered by Medicaid (dark blue = yes, light blue = no):

In several states, Medicaid has limits on the number of prescription drugs allowed (often not enough to cover all drugs needed for proper HIV care) and other healthcare factors.

Access to primary care physicians is also a problem, though not as dramatic as in rural areas. Here’s a look at “health professional shortage areas,” specifically primary care, according to HRSA:

Poverty rates in the south are rising faster than in other regions of the country. The slides above are a sampling from my talk, which in itself offers only a glimpse at the many issues involved (I’m not an expert, it should be said). But hopefully they provide some insights into a complicated and very serious problem.

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Avastin for Lung Cancer

By Jessica Wapner
Posted: April 17, 2012

One of the most interesting aspects of a newly published study of bevacizumab (Avastin) for older patients with advanced non-small cell lung cancer (NSCLC) is the abstract’s conclusion:

“Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.”

It’s refreshing to see no extra flourishes added, no unnecessary words trying to imply that somehow the drug might be of some benefit to some patients maybe. Of course better treatments are needed for older people suffering from advanced lung cancer, but there’s no use forcing a combination if it doesn’t work.

The study, conducted by several physicians at the Dana-Farbar Cancer Institute, was actually a retrospective examination. A total of 4,168 patients with NSCLC, all age 65 years or older and all Medicare beneficiaries, all diagnosed between 2002 and 2007, were split into three groups, as follows:

Group 1: Diagnosed in 2006-2007; initial chemotherapy with bevacizumab-carboplatin-paclicataxel

Group 2: Diagnosed 2006-2007; initial chemotherapy with carboplatin-paclitaxel (so same as above minus bevacizumab)

Group 3: Diagnosed 2002-2005; initial chemotherapy with carboplatin-paclitaxel

Overall survival measured from the first date of chemotherapy treatment until death, or the “censoring date” of December 31, 2009, served as the primary outcome of the study.

According to the report, just published in JAMA, the median survival estimates were:

Group 1: 9.7 months; interquartile range, 4.4–18.6
Group 2: 8.9 months; IQR, 3.5–19.3
Group 3: 8.0 months; IQR, 3.7–17.2

One-year survival probabilities were:

Group 1: 39.6% (95% confidence interval, 34.6%–45.4%)
Group 2: 40.1% (95% CI, 37.4% –43.0%)
Group 3: 35.6% (95% CI, 33.8%–37.5%)

Importantly, the authors state in the abstract: “Subgroup and sensitivity analyses for key variables did not change these findings.”

Bevacizumab is already approved for advanced NSCLC, where it is given in combination with carboplatin and paclitaxel for patients who have not received chemotherapy for advanced disease already. (The drug is also approved for the treatment of metastatic colorectal cancer, metastatic kidney cancer, and glioblastoma.) This new report seems to suggest that the triple combination for NSCLC should probably be confined to patients under 65 years of age. (NOTE: I am NOT a doctor and am not qualified to offer any opinions on cancer treatments.)

Numerous clinical trials of bevacizumab for cancer are ongoing. Some are sponsored by competitors seeking to compare their drug to a bevacizumab-containing regimen, and others are focused on combining bevacizumab with other agents such as AZD2171, temozolomide, Revlimid, and many others.

And for anyone seeking additional context about bevacizumab in the treatment of cancer, here are some of my previous posts. Looking at this list, you might begin to question the sanity of a writer so interested in a single drug. But tracing the history of this drug provides powerful insights about clinical trials, the drug development process, FDA review of new drugs, weighing benefits against side effect risks, and how to consider cost in healthcare decisions. When a single thread tells this much of a story, it’s worth following.

Avastin for Ovarian Cancer
Let the Death Panel Accusations Fly! (On the withdrawal of FDA approval of Avastin for breast cancer)
Taking a Stab at Cost-Effectiveness
The Avastin Saga

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Category: cancer, Clinical Trials | Tagged , , , , , , | 6 Comments

New Study of HIV Hot Spots

By Jessica Wapner
Posted: March 14, 2012

HIV infection rates of black women in certain parts of the United States is five times higher than the overall rate of infection among black women, according to a newly published study by the HIV Prevention Trials Network (HPTN).

The study, HPTN 064, looked at HIV rates in six geographic “hot spots”; that is, regions of the U.S. known to have elevated rates of HIV and poverty. Just how elevated are those HIV rates, the study aimed to address.

The hot spots included in the study were Atlanta, GA; Raleigh-Durham, NC; Washington, D.C.; Baltimore, MD; Newark, NJ; and New York, NY.

According to a report of the study in Infection Control Today, about a quarter of new HIV infections in the U.S. occur in women. Of these women, 66% are black—a figure that stands in stark contrast to the fact that black women account for 14% of the U.S. female population.

HPTN 064 (also called “The Women’s HIV SeroIncidence Study, which somehow qualifies for the questionable acronym “ISIS”) enrolled women ages 18 to 44 without a prior positive HIV test. The stated purpose of the study was “to estimate the overall HIV-1 incidence rate in women at risk for HIV acquisition in the US and to evaluate the feasibility of enrolling and following a cohort of these women.”

Among the 2,099 women enrolled in the study, 88% of whom were black, the HIV incidence was 0.24%. (As a measure of comparison, here is a chart showing HIV/AIDS rates in sub-Saharan Africa, though note that the rates show HIV/AIDS, not non-AIDS HIV) Enrollees in HPTN 064 were asked about their mental health, sexual behavior, history of sexually transmitted infections, domestic violence, social support, financial insecurity, and health care utilization.

Thirty-two women were found to have HIV infection at the time that they enrolled in the study; they had been previously unaware of their HIV status.

The findings of HPTN 064 have not been reported in the New York Times, the Washington Post, or the LA Times, even as an online blog item.

Among the study sites were Johns Hopkins HPTN Network Laboratory, Bronx-Lebanon Hospital Center, Harlem Prevention Center, New Jersey Medical School, Wake County Health and Human Services, University of North Carolina AIDS Clinical Trials Unit, The Ponce de Leon Center, and the Hope Clinic of the Emory Vaccine Center. The study was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

For a more graphic view of HIV/AIDS across the United States, the HIV/AIDS Atlas shows rates by county. (You have to do a quick, free registration to use the atlas.) The view is startling. Did you know that most of eastern Massachusetts has HIV rates of .174%–.309%? This is in the upper reaches of prevalence. You can also see the ultra-concentrated pockets of elevated rates around Kansas City, MO; Jackson, MI; and Little Rock, AR, among other places. In each of these areas, HIV rates are in the .174% to .309% range, while the immediately surrounding areas have much lower rates. See the bar graph on the site for a make-no-mistake view of the racial divide at play here.

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Image (showing high rates of HIV in certain areas of New Jersey) from the HIV/AIDS Atlas

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Intratumor Heterogeneity (aka, Things Have Many Parts)

By Jessica Wapner
Posted: March 9, 2012

To say that personalized medicine has hit a “bump in the road” with a study published this week in the New England Journal of Medicine reflects the expectancy that targeted drugs for cancer (or other diseases) ought to be around the corner. After all, now that we know that it’s possible to target the abnormal cellular mechanisms triggered by genetic mutations with laboratory-synthesized chemicals (Gleevec for CML, the recently approved Xalkori (generic name, crizotinib) for lung cancer), shouldn’t we just figure out the abnormalities in each kind of tumor and then create drugs to address whatever haywire situation results? Calling this study a “bump,” as the Wall Street Journal does, makes it seem as if this weren’t an entirely new field. No – this new study simply adds more to the story about genes and cancer.

Researchers from the UK’s Medical Research Council, Cancer Research UK, and other UK institutions, examined “intratumor heterogeneity.” That is, they looked at the amount of genetic variation within a single tumor. They found that more than 60% of the known somatic (ie, spontaneous, rather than inherited) genetic mutations were not present in every sample from a tumor. In other words, there is a lot of variety going on inside tumors.

That’s an enormous amount of variation. It means the odds that a tumor biopsy will contain the essential genetic information may be quite slim. It also points to the extraordinary capacity that tumors have to evolve rapidly, in part explaining why cancer often becomes resistant to whatever drug is attacking it.

The concern here is that if a researchers has a biopsy from one region of a tumor, the mutations present elsewhere in a tumor could be missed. The idea that a mutation could be seen in one sample and not another also adds another layer of difficulty to the task of sorting out which are the “driver” mutations—that is, which genetic mutations are triggering the cancer—and which mutations are more passive.

If you have tens of thousands of genes you’re working with in a particular tumor sample, sorting out the causative variations from the changes that happen as the tumor evolves is a long, arduous task. It’s for this reason that the idea of personalized medicine—and here we are talking specifically about drugs targeted against the genetic make-up of an individual cancer, not about a whole-person regimen for life based on your personal DNA quirks—is one that has to be held with a long-view. It took decades for the first useful chemotherapy drug to be discovered. If we absorb the notion that targeted therapy is still in its nascent stage, then this new study isn’t a bump in the road, but rather another description of the scenery.

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Category: cancer, Targeted Therapy | Tagged , , , , , | 1 Comment

The Story of Peyton Rous and Chicken Cancer

By Jessica Wapner
Posted: February 9, 2012

“Tumors destroy man in a unique and appalling way, as flesh of his own flesh which has somehow been rendered proliferative, rampant, predatory and ungovernable.”
Continue reading »

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How Much Money Do Drug Companies Pay the FDA?

By Jessica Wapner
Posted: January 25, 2012

The Prescription Drug User Fee Act became a law in 1992. PDUFA (or as most people say, padoofa) allows the FDA to collect fees from pharmaceutical companies filing new drug applications. A new drug application, or NDA, is the process by which the FDA reviews new drugs. Updated performance goals, which have been part of PDUFA from the start, for 2013 through 2017 were issued this past September.

PDUFA was mainly created as a response to complaints among consumers, the pharmaceutical industry and the FDA that drug approvals were taking too long. The FDA said that without more money, there would never be enough staff support to churn out approvals at a rate that met with public and industry approval, and that met the needs of patients awaiting better treatments. In that light, the arrangement seems reasonable: drug companies are private, for-profit businesses that require regulatory approval of products they want to bring to market, so it seems right that they should have to pay for the time a government agency has to spend reviewing the compound.

On the other hand, another point of view holds that PDUFA spells not just padoofa, but also trouble, because its puts the FDA in the pockets of the drug industry. In the same way that doctors are accused of subjecting themselves to bias when they receive consulting or speaker fees from a drug company, so has the FDA been accused of kowtowing to the pharmaceutical industry, approving drugs that maybe shouldn’t be approved for one reason or another, and allowing the committees assembled to review NDAs to be stacked with conflicts of interest.

All of the information about what fees are paid to the FDA is public information. But few people who have tried to navigate through the FDA’s labyrinthine website have lived to tell the tale. So, apropos of nothing, here are some of the relevant numbers.

In FY 2012, the fee for filing an NDA that requires clinical data is $1,841,500. For an application that does not require clinical data, the fee is $920,750.

The most recent year for which the payment amounts are available is 2010. In FY 2010, the total amount paid to the FDA for application fees was $172,238,150. Establishment fees (another, smaller component of PDUFA) totaled $183,328,513. Product fees (yet another, still smaller component) came to $173,709,880. (Fun task: See if you can make heads or tails of the definitions on establishment fees and product fees at this FAQ on PDUFA) That brings the grand total of PDUFA fees collected in FY 2010 to $529,276,543.

According to the FDA, this total almost covered all of the expenses associated with NDA reviews, which are: personnel compensation and benefits; travel and transportation; rent; communications; contract services; equipment and supplies; and other. In FY 2010, that total came to $573,258,400. (In 2009, the total was $512,051,400. You can see the two breakdowns here.)

Interestingly, the total number of NDAs filed in 2010 was 86, the lowest number in the past five years. However, the number of priority NDAs — applications for more urgently needed drugs, such as those to treat rare diseases with highly limited treatment options — remained steady. Approval times for priority applications was about 9 months in 2009, the most recent year with meaningful data. In 2010, the percentage of approvals made during the first cycle of review decreased for the third straight year, which might indicate a more stringent review process. (According to the FDA, about 80% of all filed applications will eventually be approved.)

In one sense, it could be said that if the branch of the FDA involved in reviewing NDAs has its budget mainly covered by PDUFA fees, rather than taxpayer dollars, the turn that part of the agency is almost like a private company. At the same time, it would seem weird if taxpayers were covering the NDA expense and then being charged again for drug purchases. Yet another tangled web woven.

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FDA image from Flickr, Creative Commons License, by marcospozo

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“A Spot on His Lung”

By Jessica Wapner
Posted: January 23, 2012

My father-in-law is from a small Greek island called Chios. Ocean breezes permeated his youth, which was spent making toy boats out of sticks and whatever else he and his friends could find, making whatever mischief he could, and fully enjoying being alive.
Continue reading »

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Avastin for Ovarian Cancer

By Jessica Wapner
Posted: January 11, 2012

You’ve probably already seen the headlines noting the disappointing outcomes of two phase III studies of bevacizumab (brand name Avastin, made by Genentech) for ovarian cancer. I’ve been trying to familiarize myself with the data this morning—I am pretty certain that practicing interpreting study reports can add years to my brain functioning—and figured I’d post a quick summary here.

There were two phase III studies published in the New England Journal of Medicine on December 29. (And don’t you want to know how that came about? Were the studies planned from the get-go to end at around the same time? Or were the analyses specifically timed to be reported simultaneously? And were there women with ovarian cancer being treated with Avastin off-label in the meantime, while these studies, funded in part by public dollars, were being prepared for publication?) One study looked at a couple of different ways of incorporating the drug into primary treatment. The other study was a direct comparison of two regimens.

First, the more complicated trial. Here, 1,873 women with stage III or IV ovarian cancer were randomly assigned (double-blind) to one of three groups:

Group 1: Chemotherapy in cycles 1–6, with a placebo added for cycles 2–22.
Group 2: Chemotherapy plus bevacizumab, cycles 2–6; chemotherapy plus placebo, cycles 7–22
Group 3: Chemotherapy plus bevacizumab, cycles 2–22

The primary endpoint was progression-free survival. Maybe this is common knowledge by now, but in case not, let’s remember that PFS is not a measure of real benefit. Rather, it’s a surrogate marker, indicating a potential for actual benefit. The real benefit would be if the addition of bevacizumab improved overall survival by a clinically meaningful amount of time. PFS does not necessarily indicate (in fact, it rarely indicates) an extension in actual survival time.

But, the primary endpoint was PFS, so here are those numbers. For group 1, the median PFS was 10.3 months. Group 2 was 11.2 months, and Group 3 was 14.1 months. The study duration was for up to 10 months. The authors note that there was no significant different in overall survival at the time the data were analyzed, although it’s important to remember that OS wasn’t the primary endpoint, so even a negative outcome there isn’t necessarily meaningful. And the rate of hypertension requiring medical intervention was at least double among women receiving bevacizumab (7.2% for Group 1, 16.5% for Group 2, and 22.9% for Group 3).

The conclusion in the study’s abstract is interesting. It reads:

The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer.

Would you agree with that statement, based on the numbers above?

Now, the other study. Here, 1,528 women from 11 countries were treated with either carboplatin + paclitaxel, or this chemotherapy combination plus bevacizumab. I haven’t read the full study, only the abstract, so I don’t know what the primary endpoint, determined before the study launched, was intended to be. However, the abstract states that the outcome measures were PFS analyzed per protocol, then PFS updated, and interim overall survival. From this, I’d infer that the primary endpoint was PFS at 36 months (the updated PFS was at 42 months).

So, the results. PFS at 36 months for the control arm (standard chemotherapy) was 20.3 months, meaning that women receiving combination chemotherapy went for, on average, 20.3 months without cancer progressing. Women who received chemotherapy + bevacizumab experienced disease progression at a median 21.8 months. At 42 months, the PFS was 22.4 months and 24.1 months, respectively.

The authors also provide a subset analysis for women who were at high risk for progression when they enrolled in the study; that was about 30% of the study population. Among this group, PFS at 42 months was 14.5 and 18.1 months, respectively. Overall survival for these women was 28.8 months and 36.6 months, respectively.

The abstract conclusion for this study reads:

Bevacizumab improved progression-free survival in women with ovarian cancer. The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression.

Again, would you agree with that statement? Here is a great example of distinguishing between numbers that are statistically significant and numbers that are clinically meaningful.

Many news outlets reported on these studies. One interesting article by the Los Angeles Times provided a look at the cost of this treatment. This article (a blog post, actually) draws on a study from the Journal of Clinical Oncology (JCO) analyzing the cost-effectiveness of bevacizumab in ovarian cancer. This study was published back in April 2011, six months before the NEJM reports of these two phase 3 trials.

The JCO cost-effectiveness analysis was based on preliminary data from the three-group study discussed above (the trial is also known as Gynecology Oncology Group, or GOG, 218). The cost analysis estimated the cost of treating 600 patients on each arm of that study, using the baseline estimates of PFS and also bowel perforation, a side effect of bevacizumab. According to the analysis, the cost of treating women who received chemotherapy alone was $2.5 million. The cost for Group 2 was $21.4 million. The cost for Group 3 was $78.3 million. According to these numbers, the “incremental cost effectiveness ratio”—which measures the cost per year of progression-free life saved—was over $400,000 for both bevacizumab-containing groups. Reducing the cost of this drug by 25% brought that number down to $100,000 for Group 3. But, treatment of bowel perforation adds costs that drive that figure back up.

That cost-effectiveness analysis concluded:

The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.

You can have nothing but compassion for anyone experiencing ovarian cancer, and women with this disease are definitely in need of improved treatments. It appears that bevacizumab probably isn’t next on the horizon, though.

All that being said, you have to wonder if the search for biomarkers that might indicate the likelihood of someone benefiting from Avastin will yield fruit. Time will tell. But it might be a long, long time.

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Category: cancer, Drug Development | Tagged , , , , | 3 Comments

Sharing News

By Jessica Wapner
Posted: January 9, 2012

Hello out there, and happy 2012.

Work in Progress has gone a little quiet lately, and that will change soon. Though not today. In the meantime, I wanted to share some nice news, which is that my book-in-progress is now official. “The Philadelphia Chromosome – The Epic Quest to Tame a Single Deadly Gene” will be published in Spring 2013 by The Experiment, a NY-based independent publishing company.

This story will chart the forty years of pathbreaking discoveries that first unraveled the link between DNA and cancer, and the subsequent struggle to bring to market the drug that cures one particularly deadly cancer (chronic myelogenous leukemia).

Many readers of this here blog will be familiar with some parts of this story; in particular, the development of Gleevec and some of the tales of woe and heroism that led to this drug’s success and blockbuster status. But there is so much more to tell. So, so, so much more – from the first spotting of the Ph mutation in 1959, back in time to how science figured out that humans have 46 chromosomes (a fascinating story in its own right that involves castrated patients from psychiatric institutes among other strange facts, twists, and turns), and into the advent of personalized medicine, or at least our fixation with its potential. Most importantly, this story provides a clear-eyed, behind-the-scenes look at how drugs are made: the science, the medicine, the money, the bureaucracy, and all of the other very human aspects that guide the bringing of a new medicine into the world.

I am totally jazzed, thrilled to the gills, and over the moon to have a chance to put it all down on paper. After living with a book proposal for almost five years, I’m still pinching myself. Now the task is to do the story justice. It’s an incredible tale that has so much relevance to our world today.

Thanks for reading this little update. I’ll still be posting here regularly, hopefully even more frequently, during the next few months, so – more soon.

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