Drugs Show Promise Slowing Advanced Melanoma

The drugs represent success in two new approaches to combating cancer: one by attacking a specific genetic mutation that accelerates tumor growth; the other by unleashing the body’s immune system to fight the disease

“This is an unprecedented time of celebration for our patients,” Dr. Lynn M. Schuchter, a melanoma specialist at the University of Pennsylvania, told reporters Sunday in Chicago at the annual meeting of the American Society of Clinical Oncology, where the results were presented.

The drugs do not cure melanoma, except perhaps in rare cases. But experts said they might add two to several months to the expected lifespans of people with advanced melanoma. Right now people with metastatic melanoma — meaning it has spread to distant organs — typically live 6 to 10 months.

In one trial, 84 percent of patients taking the experimental drug vemurafenib (pronounced vem-yoo-RAF-en-ib) were still alive after six months, compared with 64 percent of those getting an older chemotherapy drug, dacarbazine. Using another statistical measure, the risk of dying was reduced 63 percent.

The effect was so marked that the trial was stopped early for ethical reasons, so that patients in the control group could be offered the new drug. Because of that, researchers do not yet know the median survival.

“You don’t need to wait for 50 percent of 675 patients to die to conclude that one drug is much better than the other,” said Dr. Antoni Ribas of the University of California, Los Angeles, who was an investigator in the trial and has been a consultant to the developer of the drug.

The other new drug, ipilimumab (pronounced ip-ee-LIM-yoo-mab), when combined with dacarbazine, extended median survival to 11.2 months compared with 9.1 months for those who received dacarbazine alone. After three years, 20.8 percent of those who got that new drug were alive, compared with 12.2 percent of those in the control group.

The results of both trials were published online by The New England Journal of Medicine in addition to being presented here.

To be sure, more than half of patients with metastatic melanoma would not be helped all that much by either drug. Experts say more needs to be done, especially since melanoma affects more young adults than many other types of cancer.

Even if the new drugs allow patients with metastatic melanoma to live two years, “Two years is nothing when you’re 30,” said Dr. Anna C. Pavlick, head of the melanoma program at New York University.

Still, doctors and patient groups welcomed the progress because until now treatment of melanoma that had spread beyond the skin to distant organs “was terrible even by routine cancer standards,” said Dr. Vernon K. Sondak, chairman of cutaneous oncology at the Moffitt Cancer Center in Tampa, Fla.

Also, the number of melanoma cases has been rising, unlike for many other types of cancer. Doctors say that is because of unprotected sun exposure years ago, the proliferation of tanning salons and perhaps more attention to detecting the disease.

There were about 68,000 new cases of melanoma and about 8,700 deaths last year in the United States, up from 48,000 cases and 7,700 deaths in 2000, according to the American Cancer Society. Particularly fast increases have occurred among people older than 65 and among women 15 to 39 years old.

Vemurafenib is the latest so-called targeted therapy, which inhibits the effects of genetic mutations that spur tumor growth and spread. In particular, the drug counters the effect of a mutation in a gene called B-RAF that was discovered in 2002 to be common in melanomas. (The drug’s name comes from V600E mutation in RAF.)

The drug, which is taken orally twice a day, would be used only by the roughly half of melanoma patients whose tumors have this mutation. The drug significantly shrinks tumors in about half of these patients — or about a quarter of all melanoma patients.

It was developed by Roche and Plexxikon, a biotechnology company in Berkeley, Calif., that was recently acquired by Daiichi Sankyo of Japan. The drug is expected to be approved by the Food and Drug Administration within a few months.

Ipilimumab, the other new drug, releases a brake on the body’s immune system, allowing it to more effectively attack the tumor. Developed by Bristol-Myers Squibb, it was approved in March and is sold under the name Yervoy.

A series of articles in The New York Times last year followed the development of vemurafenib, then known as PLX4032, and recounted how some patients close to death seemed to make miraculous recoveries.

The effect, however, typically lasts only about seven months before the cancer starts to grow again, though some patients benefit for more than two years.

S. Taylor Chance, a 67-year-old real estate agent in Rancho Cucamonga, Calif., has been taking vemurafenib in a clinical trial since March 2010. “If it weren’t for the trial I wouldn’t be here,” she said.

It has not been all good. Ms. Chance said the drug caused such extreme pain at one point that “I called in the children and said, ‘I’m done, I can’t do this any more.’?” But she had her dose reduced and took other medications for the pain.

In the trial, sponsored by Roche and led by Dr. Paul B. Chapman of the Memorial Sloan-Kettering Cancer Center in New York, 38 percent of participants had to stop taking the drug or lower the dose because of side effects, including rash and joint pain. Many patients get minor skin cancers that can be removed by dermatologists.

The trial of ipilimumab, paid for by Bristol-Myers, involved 502 patients with late-stage melanoma.

Last year at this conference, researchers presented results of a trial showing a survival advantage for patients who had undergone a previous treatment. The new trial of this drug, by contrast, involved patients who were getting treated for the first time.

While the extension of median survival of two months, from about 9 months to about 11 months, was less than some experts expected, researchers said the real benefit was that a small number of patients, perhaps 10 to 20 percent, could live a long time.

Because it unleashes the immune system, ipilimumab can have serious side effects. In the latest trial, a big one was liver damage.

A course of treatment of ipilimumab costs $120,000. The price of vemurafenib has not been announced, but is expected to be at least tens of thousands of dollars per year.

Doctors are eager to try the two drugs together. Roche and Bristol-Myers said Thursday that they would conduct such tests.

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Promise of Arab Uprisings Is Threatened by Divisions

。  Khaled Elfiqi/European Pressphoto AgencyEgyptian protesters displayed giant flags, one representing all Arab countries, during a unity rally in Cairo's Tahrir Square on May 13.

BEIRUT, Lebanon — The revolutions and revolts in the Arab world, playing out over just a few months across two continents, have proved so inspirational to so many because they offer a new sense of national identity built on the idea of citizenship.

var _obj = new NYTMM.FadingSlideShow($("nytmm_embed947"),190,126,chameleonData); _obj.setPhotoData(chameleonData.photos); Video interviews with more than two dozen people under 30, from Libya to the West Bank, talking about their generation’s moment in history and prospects for the future.

Riot police clashed with protesters in Tunis on May 6.

But in the past weeks, the specter of divisions — religion in Egypt, fundamentalism in Tunisia, sect in Syria and Bahrain, clan in Libya — has threatened uprisings that once seemed to promise to resolve questions that have vexed the Arab world since the colonialism era.

From the fetid alleys of Imbaba, the Cairo neighborhood where Muslims and Christians have fought street battles, to the Syrian countryside, where a particularly deadly crackdown has raised fears of sectarian score-settling, the question of identity may help determine whether the Arab Spring flowers or withers. Can the revolts forge alternative ways to cope with the Arab world’s variety of clans, sects, ethnicities and religions?

The old examples have been largely of failure: the rule of strongmen in Egypt, Syria, Libya and Yemen; a fragile equilibrium of fractious communities in Lebanon and Iraq; the repressive paternalism of the Persian Gulf, where oil revenues are used to buy loyalty.

“I think the revolutions in a way, in a distant way, are hoping to retrieve” this sense of national identity, said Sadiq al-Azm, a prominent Syrian intellectual living in Beirut.

“The costs otherwise would be disintegration, strife and civil war,” Mr. Azm said. “And this was very clear in Iraq.”

In an arc of revolts and revolution, that idea of a broader citizenship is being tested as the enforced silence of repression gives way to the cacophony of diversity. Security and stability were the justification that strongmen in the Arab world offered for repression, often with the sanction of the United States; the essence of the protests in the Arab Spring is that people can imagine an alternative.

But even activists admit that the region so far has no model that enshrines diversity and tolerance without breaking down along more divisive identities.

In Tunisia, a relatively homogenous country with a well-educated population, fault lines have emerged between the secular-minded coasts and the more religious and traditional inland.

The tensions shook the nascent revolution there this month when a former interim interior minister, Farhat Rajhi, suggested in an online interview that the coastal elite, long dominant in the government, would never accept an electoral victory by Tunisia’s Islamist party, Ennahda, which draws most of its support inland.

“Politics was in the hands of the people of the coast since the start of Tunisia,” Mr. Rajhi said. “If the situation is reversed now, they are not ready to give up ruling.” He warned that Tunisian officials from the old government were preparing a military coup if the Islamists won elections in July. “If Ennahda rules, there will be a military regime.”

In response, protesters poured back out into the streets of Tunis for four days of demonstrations calling for a new revolution. The police beat them back with batons and tear gas, arrested more than 200 protesters and imposed a curfew on the city.

In Cairo, the sense of national identity that surged at the moment of revolution — when hundreds of thousands of people of all faiths celebrated in Tahrir Square with chants of “Hold your head high, you are an Egyptian”— has given way to a week of religious violence pitting the Coptic Christian minority against their Muslim neighbors, reflecting long-smoldering tensions that an authoritarian state may have muted, or let fester.

At a rally this month in Tahrir Square to call for unity, Coptic Christians were conspicuously absent, thousands of them gathering nearby for a rally of their own. And even among some Muslims at the unity rally, suspicions were pronounced.

Anthony Shadid reported from Beirut, and David D. Kirkpatrick from Cairo. Heba Afify contributed reporting from Cairo, and an employee of The New York Times from Damascus, Syria.

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The Promise of Rapture for the High-Tech Elite

Ray Kurzweil, the influential technologist, came to the Palace of Fine Arts theater in San Francisco a few days ago to promote his vision of “the Singularity.” One attendee admiringly described it as “the cult Rapture of the Nerds.”

It was a much more fitting prelude to the Easter holidays than Mr. Kurzweil would like to think.

The Singularity, as he explains it, is a point in the near future when rapidly escalating technological advances will allow the most evolved humans (i.e., Mr. Kurzweil and his early-adopting followers) to incorporate technology into their bodies. Doing so will allow them to live hundreds of years and perhaps forever. Mr. Kurzweil wrote a book on the subject in 2005 and has been proselytizing ever since. The quick sell: Join me in outsmarting death.

This vision has obvious appeal to the Silicon Valley set, which holds sacred the belief that technology can solve most any problem; Google’s co-founder Larry Page, and a long list of other tech celebrities, helped establish Singularity University, where rich or deep-thinking techies try to get an edge on the future.

New Agers, too, find something alluring in the idea of man transcending the mere self and attaching to a more grandiose vision of the human project.

Yet there is a flip side to the Singularity, a distinctly unmodern religiosity of the sort that often horrifies high-powered engineers and sophisticated citizens of the New Economy. Mr. Kurzweil offers the best of both worlds, as it were: an answer to existential questions and the ageless quest for immortality, wrapped in a package of science and innovation.

Michael Lindvall, a theologian and pastor of Brick Presbyterian Church in New York, pegs Mr. Kurzweil’s Singularity dogma as a modern iteration of the Gnosticism prevalent in the second and third centuries.

Gnosticism “was basically the idea that people save themselves by being smart,” Mr. Lindvall said. “By knowing these secret things, you would become cognoscenti, one of the few, elitist. Gnostics looked down on the hoi polloi Christian masses.”

Kevin Kelly, a co-founder of Wired magazine and an influential technology theorist himself, is not an adherent of the Singularity, but has spoken at length with Mr. Kurzweil about it and certainly sees the appeal.

“It attracts people who are scientific, rational, not religious,” Mr. Kelly said, “and it offers them the same comforting idea that heaven offers to someone more religious.”

Mr. Kurzweil said, via e-mail, that any comparison of Singularity to religion was “incorrect.”

“Religions emerged in pre-scientific times” he wrote, and are “based on faith and not science.”

“We need to update our understanding of the destiny of our human-machine civilization based on what science now tells us,” he added. “The bottom line is that my thesis is based on a detailed scientific analysis of the history of technology and not on faith.”

Certainly, some of Mr. Kurzweil’s adherents seemed overcome with religious fervor at his recent San Francisco appearance. “His fans notoriously swarm the stage, like they are doing here!” an event organizer barked at other staff members during a V.I.P. reception, warning them to be alert.

Mr. Kurzweil predicts the Singularity will occur in about 2040. Mr. Kelly suggests he so tirelessly promotes it in hopes of speeding things along. In 2040, Mr. Kurzweil would be 92. He obsesses over his diet and consumes 150 pills a day to stave off aging.

Thoughts of mortality produce “profoundly sad and lonely feelings,” Mr. Kurzweil said in “Transcendent Man,” a filmed accompaniment to his live presentation. “So I go back to thinking about how I’m not going to die.” (The German words “kurz weil,” by the way, translate into “short time,” so perhaps Mr. Kurzweil was predestined to obsess over ways to extend his life.)

Ken Marks, a local mathematician, was one of 700 or so who came to hear Mr. Kurzweil — and he was skeptical about the whole thing. His objections were scientific, rather than theological, saying that the Singularity ignored the scientific principle of complementary pairs. Like space and time, or electric force and magnetic force, “death and life are a complementary pair,” Mr. Marks said. “Death is intrinsic to life.”

“If you do not have death, you do not have life,” he said.

Mr. Kelly suggests such scientific nitpicking wouldn’t hold much sway with Mr. Kurzweil, though he, too, is a man of science.

“The remarkable thing about Ray is that he has no doubt,” Mr. Kelly said. “He has an answer for every objection. His certainty is unwavering.”

Is that faith, in the traditional sense? “Exactly,” Mr. Kelly said. “He has faith.”

 

Income Slips For Yahoo, But Ads Show Some Promise

SAN FRANCISCO — Carol A. Bartz, Yahoo’s chief executive, still has work ahead to lift her company out of its slump.

That reality was underscored on Tuesday when Yahoo reported its first-quarter earnings, which showed promising signs in the company’s main business — display advertising — but troubles in search. The mixed results do little to appease critics of Ms. Bartz’s turnaround plan, which she put in place soon after joining Yahoo two years ago.

Ms. Bartz is trying cut costs and build on the company’s strength in online editorial content. But it continues to trail faster-growing rivals like Google and Facebook.

The center of her turnaround effort, Yahoo’s display advertising business, grew 10 percent, to $471 million, compared with the quarter a year ago. The sector, which includes banner ads, is one of the company’s bright spots.

On a conference call with analysts, Ms. Bartz said Yahoo was making “tangible progress,” and that “over all, our turnaround is proceeding on schedule.” She cited higher traffic to a number of Yahoo’s media properties like its news blogs, and its coverage of the Academy Awards.

But Yahoo’s other businesses contracted, particularly search, which is operated by Microsoft through a partnership. Revenue from search, after payments to Microsoft and others, fell 19 percent, to $357 million.

Ms. Bartz acknowledged in the call that the Microsoft partnership, a prominent deal when it was announced two years ago, has not met expectations. Technical complications have made the revenue the two partners collect per search decline since their search engines were combined.

Still, Yahoo said it would receive a guaranteed minimum payment from Microsoft for the next year in the United States, regardless of how search advertising performs. After that, the payments may decline if the problems are not fixed. “We are working very close with Microsoft on these issues,” Ms. Bartz said.

Yahoo’s net income in the quarter fell 28 percent, to $223 million, or 17 cents a share, compared with $312 million, or 22 cents, in the year-ago quarter. The comparison is complicated by the sale last year of Zimbra, an e-mail company, which had lifted Yahoo’s 2010 first-quarter profit.

Yahoo said revenue in the quarter fell 24 percent, to $1.21 billion, from $1.6 billion. Selling and discontinuing some products as well as outsourcing search businesses to Microsoft contributed to the decline.

Excluding commissions paid to advertising partners, revenue was $1.06 billion, matching what analysts had expected.

For its part, Google reported a 27 percent increase in first-quarter revenue.

Yahoo is losing ground in online ad spending. Its share is expected to drop 1.5 percentage points to 11.9 percent this year, according to eMarketer.

Yun Kim, an analyst with Gleacher & Company, said he was happy Yahoo at least matched expectations and did not issue a disappointing forecast. There may be a lot of focus on Yahoo’s troubles with search, he said, but its future depends on its ability to entice advertisers into long-term deals for display ads.

“There’s still a lot of work to be done there,” Mr. Kim said. “The inflection point whether they are going to make things happen will come in the second half of the year.”

A major area of concern is the Americas, Yahoo’s biggest source of revenue, Mr. Kim said. Revenue in the region excluding payments to partners has declined for nearly two and half years, and that erosion accelerated in the first quarter, to 11 percent, compared with single digits in recent quarters, he said.

Ms. Bartz, who has laid off hundreds of employees and ended several products that failed to catch on, has kept operational expenses in check. They fell 8 percent, to $647 million.

Last week, investors punished Google for letting operational expenses grow 55 percent in the first quarter, from newly hired employees and salary increases for its entire work force.

Shares of Yahoo rose 1.7 percent, to $16.40, in after-hours trading on Tuesday after its results beat the low expectations set by analysts. During regular trading, shares fell 1.4 percent, to $16.12.

For the second quarter, Yahoo said it expected that revenue excluding payments to advertising partners would be $1.075 billion to $1.125 billion. Income excluding certain items is expected to be $160 million to $190 million.