Friday, May 29, 2015

Genetic glitch can predict response to new class of cancer drugs

<span id="midArticle_start"/><span id="midArticle_0"/> May 29 Patients with colon and othercancers who have a specific defect in genes needed for DNArepair are far more likely to respond to a new class of drugssuch as Merck & Co's Keytruda, which enlist the immunesystem to attack tumors, a new study has shown.

<span id="midArticle_1"/>The small study, financed not by Big Pharma but by swimmerswho raised charitable donations, tested Keytruda in patientswith advanced colon and rectal cancers and found 92 percent ofpatients with the genetic defect had their disease controlledcompared with 16 percent who did not carry the defect.

<span id="midArticle_2"/>The findings, announced on Friday at the American Society ofClinical Oncology (ASCO) meeting in Chicago, point to a new wayto predict who will respond to the treatments, which are knownas PD-1 inhibitors and can cost $150,000 a year.

<span id="midArticle_3"/>"Conservatively speaking, we think this would help 2 to 3 percent of all cancer patients," said Dr. Luis Diaz of theLudwig Center at Johns Hopkins Kimmel Cancer Center inBaltimore, whose study was also published online in the NewEngland Journal of Medicine.

<span id="midArticle_4"/>"These are patients with metastatic disease that wouldn'thave any other alternatives."

<span id="midArticle_5"/>The results come courtesy of some 500 Baltimore swimmers whoraised money for the study by taking a chilly dip last fall intoa river leading to the Chesapeake Bay.

<span id="midArticle_6"/> <span class="first-article-divide"/>The study involved patients with defects in the machineryneeded for fixing mistakes in DNA. Individuals with thesedefects develop tumors teeming with mutations, as many as 20times more than cancer patients with working copies of theserepair genes.

<span id="midArticle_7"/>Since the immune system is trained to recognize foreigninvaders, Hopkins researchers hypothesized that patients withtumors loaded with mutations might have a more robust responseto cancer drugs that rev up the immune system, such as Merck'sKeytruda or Bristol-Myers Squibb's Opdivo.

<span id="midArticle_8"/>Diaz said he and Hopkins colleague Dr. Dung Le proposed thetrial to several drugmakers who refused to pay for it. Merckdonated the study drug but the researchers had to raise moneyfor the trial on their own. They turned to Swim Across America,which raises funds for cancer research.

<span id="midArticle_9"/> <span class="second-article-divide"/>The scientists have tested Keytruda in 48 patients. Among 13patients with advanced colon and rectal cancers and DNA repairdefects, eight had partial responses, meaning their cancersshrank by at least 30 percent, and four had prolonged stabledisease, resulting in a 92 percent disease control rate.

<span id="midArticle_10"/>A group of 25 patients with similar cancers who did not haveDNA repair defects showed zero response.

<span id="midArticle_11"/>In a third group of patients with a variety of other cancerswho tested positive for the DNA repair defects, six of 10responded.

<span id="midArticle_12"/> <span class="third-article-divide"/>Many of the responses lasted over a year, which isimpressive considering the study was done in patients whose"life expectancy was measured in weeks to months," Le said.

<span id="midArticle_13"/>Dr. Lynn Schuchter, an ASCO spokeswoman and a University ofPennsylvania oncologist who was not involved in the trial, saidthe findings need to be confirmed in a larger study but providean important explanation of why some patients have remarkableresponses to these treatments and others do not.

<span id="midArticle_14"/>For Adrienne Skinner of Larchmont, New York, the study was alast-ditch option after she failed to respond to two types ofchemotherapy to treat her rare gastrointestinal cancer.

<span id="midArticle_15"/>When she started treatment with Keytruda, her cancer hadspread to her liver, making it inoperable. She has now been onthe therapy for 13 months.

<span id="midArticle_16"/>"There is no tumor. I don't have to have surgery. It'sphenomenal." (Reporting by Julie Steenhuysen; Editing by Michele Gershbergand James Dalgleish)

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