Blood test helps target Roche/OSI lung cancer drug

Testing for specific cancer protein markers in lung cancer patients' blood helps find those more likely to respond to Tarceva, a drug sold by Roche and OSI Pharmaceuticals , data showed on Friday.

A study presented at the European Lung Cancer Conference in Geneva showed that a relatively simple blood analysis known as a proteomic test can identify patients whose tumours are likely to shrink with the drug -- one of a class called EGFR-blockers.

"The bottom line is that the proteomic test -- comparing 'good' and 'poor' profiles -- was strongly prognostic," David Carbone from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, who led the study, said in a statement.

"Proteomics 'good' patients also had a significantly higher response rate than proteomics 'poor' patients."

Tarceva, known generically as erlotinib, is sold by OSI and Roche and is designed to block EGFR, a gene that is overactive in many types of cancer cells.

Other drugs in the same class include AstraZeneca's lung cancer medicine Iressa, and colon cancer drugs Vectibix from Amgen and Erbitux -- sold by Bristol-Myers Squibb , Eli Lilly and Merck KGaA .

Lung cancer is the biggest cancer killer around the world, killing 1.2 million people a year. Only 15 percent of people diagnosed with lung cancer are still alive five years later.

Patients can already be tested to see if they have the right type of genetic profile to respond well to EGFR-blocking drugs, but the methods involve gene sequencing, which is complex and expensive, or a technique called fluorescence in-situ hybridization (FISH), which requires a sample of tumour tissue.

Carbone said FISH was a better predictor of benefit for Tarceva, but noted it can only be done with enough of a tissue sample.

In this study, tumour samples were only available in 22 percent of patients, he said, while 99 percent of patients were able to be successfully assessed with the proteomic test. "This (proteomic) test ... may be of particular value for those in whom tumour tissue is inadequate or unavailable," Carbone said.

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Roche Presents Several Abstracts for New Targeted Cancer Drugs at ASCO

Roche presented several studies supporting new combination treatments with Herceptin in stomach cancer and in metastatic breast cancer and reported promising data on an investigational pharmacogenomics-guided melanoma treatment at the American Society for Clinical Oncology's annual meeting here this week.

At the meeting, Roche presented data from a pivotal study showing Herceptin (trastuzumab) had a survival benefit in stomach cancer patients; results from a Phase II efficacy trial combining Herceptin and the cell-killing agent DM1 that showed treatment benefit in breast cancer patients who had failed treatment with two or more HER2-targeted treatments; and discussed the potential of developing PLX4032, a drug that targets BRAF-mutated tumors in melanoma, with a companion diagnostic.

Herceptin in Stomach Cancer

Herceptin's indication may extend into gastric cancer, according to the results of a Phase III trial presented by Roche at ASCO.

Results from the first randomized, prospectively-designed, multi-center Phase III study looking at the safety and efficacy of Herceptin in HER2-positive stomach cancer showed that trastuzumab in combination with chemotherapy is "superior" to chemotherapy alone.

"This first randomized trial investigating anti-HER2 therapy in advanced gastric cancer showed that Herceptin plus chemotherapy is superior to chemotherapy alone," Van Cutsem et al. concluded in their abstract. "The overall survival benefit indicates that Herceptin is a new, effective, and well-tolerated treatment for HER2-positive gastric cancer."

The study, called ToGa (for trastuzumab in gastric cancer), randomized 594 patients with HER2-positive gastroesophageal and gastric adenocarcinoma to receive Herceptin plus chemotherapy (5-fluorouracil or capecitabine and cisplatin) or chemotherapy alone for six cycles.

The primary end point for the study was overall survival; secondary end points included overall response rate, progression-free survival, time to progression, duration of response, and safety. An interim analysis was planned at 75 percent of deaths. According to Roche, an independent data monitoring committee recommended releasing the data when the pre-specified boundary was exceeded and median follow-up of patients reached 17.1 months.

Researchers initially tested the tumors from 3,807 patients for HER2 status, and determined that 22 percent were HER2 positive. Then 594 patients were randomized at various sites in Europe, Latin America, and Asia.

The results showed that medial overall survival "significantly improved" for patients on the trastuzumab/chemo combination versus those on just chemo. The objective response rate was 47 percent in the trastuzumab/chemo arm and 35 percent in the chemo arm.

According to researchers, the safety profile was similar in both arms of the study, with "no unexpected adverse events in the trastuzumab/chemo arm." Also, while there was no difference in symptomatic congestive heart failure between arms, researchers noted, asymptomatic left ventricular ejection fraction decreases were reported in 5 percent of the patients receiving the combination treatment versus 1 percent in those receiving chemotherapy.

"Advanced GC is an incurable disease; new and less toxic treatments are needed," the study authors noted in their abstract, adding that HER2 overexpression has been reported in between 6 percent and 35 percent of stomach and gastroesophageal tumors.

Herceptin is developed by Genentech, which operates under Roche. Genentech markets the drug inside the US, while Roche is responsible for marketing in international markets.

Herceptin is currently approved in the US as a single agent and in combination with various chemotherapy regimens for the treatment of adjuvant treatment of HER2-overexpressing breast cancer and for the treatment of metastatic breast cancer.

T-DMI

Roche presented final efficacy results from a Phase II study of a new antibody-drug conjugate, T-DMI (trastuzumab plus DMI), that has shown treatment benefit in metastatic breast cancer patients whose cancer had progressed despite treatment with two or more HER2-targeted therapies.

In the study, by Krop et al., researchers looked at the correlation between patient response to T-DMI and HER2 status in 112 metastatic breast cancer patients. HER2 status was established in patients by fluorescent in situ hybridization, immunohistochemistry, mRNA quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay.

In the trial, 107 patients were evaluable for efficacy at median 4.4 months follow-up. Of these patients 42 or 39 percent had partial responses on T-DM1. Out of 86 patients centrally tested, 64 were HER2 positive and 15 were HER2 negative, as confirmed by FISH and/or IHC. Half of 64 HER2-positive and 13 percent of 15 HER2-negative patients had partial responses.

Among 39 HER2-positive patients who were efficacy-evaluable with qRT-PCR data, 68 percent had partial responses above median levels while 35 percent had partial responses below median levels.

"HER2-positive patients had better responses to T-DM1 than HER2-negative patients, although a small number of partial responses were observed in HER2-negative patients," the study authors reported. "Assessment of HER2 expression by qRT-PCR may identify patients more likely to respond to T-DM1 therapy."

DM1 is developed by ImmunoGen. Genentech and Roche are conducting a broad clinical program with T-DM1 in HER2-positive breast cancer.

According to Roche, a Phase III study evaluating T-DM1 for second-line advanced HER2-positive breast cancer was initiated this year.

New Rx/Dx Product in Melanoma?

Roche is developing a new drug with partner Plexxikon, referred to as PLX4032/R7204. At ASCO's annual meeting, Roche presented data from a Phase I dose-escalation trial that showed the investigational agent was efficacious in a number of cancers linked to expression of mutated BRAF protein.

According to the abstract by Flaherty et al., dose escalation of PLX4032 reached dose-limiting toxicities at 1120 mg BID. The maximum tolerated dose was found to be 720 mg BID. However, researchers suggested future studies should look at how patients tolerate 960 mg BID.

"PLX4032 exhibits anti-tumor activity in V600E BRAF mutant tumors," the authors concluded. "These observations confirm that V600E BRAF is a valid therapeutic target in human cancer."

BRAF-mutated tumors occur in 60 percent of melanomas and are present in 8 percent of solid tumors. Based on the Phase I study results, PLX4032 could enter registration trials for malignant melanoma later this year, Roche said in a statement.

"If successful in treating melanoma, PLX4032 is expected to be launched with a companion diagnostic," according to Roche. The companion diagnostic would also be co-developed by Roche and Plexxikon.

Source : www.genomeweb.com

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Novartis, Roche unveil promising cancer drugs data

Swiss drugmaker Novartis AG said late stage data showed its Sandostatin LAR drug helped fight tumuors of the mid-gut, while other drugs showed benefits for treating advanced melanoma.

Novartis' rival Roche Holding AG also said on Thursday a new drug helped shrink the tumours of 25 percent of women with HER2-positive breast cancer, according to data from a mid-stage clinical trial.

Cancer drugs are seen as a key growth area for pharmaceutical makers like the two Swiss companies, which along with many others are presenting data on cancer drugs at an American Society of Clinical Oncology (ASCO) meeting.

Novartis said a Phase III study showed Sandostatin LAR more than doubled time without tumour growth and reduced the risk of disease progression by 67 percent.

It also said mid stage data on two of its drugs showed potential as treatments for advanced melanoma. Favourable results from a study into the drug Glivec mean the study will continue to a second expanded stage of enrolment.

The Swiss company also presented preliminary results which showed that 72 percent of melanoma patients treated with Afinitor combined with Roche's Avastin experienced a clinical benefit.

Afinitor, one of Novartis' most important new drugs, also helped patients with advanced liver cancer in an early stage trial.

Data from a mid stage trial of the new treatment from Roche, a combination of its Herceptin and chemotherapy known as trastuzumab-DM1, showed about 35 percent of a total 112 patients had their tumours shrink, or their disease stabilise for at least six months.

Source : www.reuters.com

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Roche’s Avastin Backed by U.S. Panel for Brain Cancer

Roche Holding AG won the backing of a U.S. panel to expand use of the blockbuster drug Avastin, acquired with the purchase last week of Genentech Inc., to patients with a deadly form of brain cancer.

Outside advisers to the U.S. Food and Drug Administration voted 10-0 today in Silver Spring, Maryland, to recommend the medicine be approved for the treatment of glioblastoma multiforme, an incurable brain cancer. About 10,000 Americans are diagnosed with the disease each year, Genentech has said.

If approved, Avastin would be the first new drug cleared for relapsed brain tumors in more than a decade, Roche said previously. The Basel, Switzerland-based company said it will conduct a large study that aims to capture more definitive data on the drug’s benefits. That helped cement the panel’s endorsement of the new use and speeding up the approval process.

“My vote is a bet on the success of the randomized trial that is planned,” said Frederick Barker, associate visiting neurosurgeon of the Massachusetts General Hospital in Boston and a member of the Oncologic Drugs Advisory Committee.

U.S. regulators are expected to rule by May 5, said Kristina Becker, a spokeswoman for Roche’s Genentech, in a telephone interview. The company markets Avastin for advanced cancers of the colon, lung and breast.

FDA staff, conducting a review in advance of today’s meeting, had questioned whether brain scans used by Roche’s Genentech were enough to show Avastin slowed tumor progression.

Stable Tumor

The panel’s vote followed a morning presentation of company data and an afternoon of testimony from patients with brain cancer, their families and advocates.

“If it wasn’t for Avastin, I wouldn’t be here today,” said Richard Oropeza Jr. of Williamsburg, Virginia, a retired program manager for the U.S. Navy, in testimony before the panel. Diagnosed in February 2006, he was given nine to 12 months to live. Now that he’s receiving Avastin infusions, his tumor is stable and not growing, said his wife, Ann Levy- Oropeza. “Thanks for giving us hope,” she said.

David Schenkein, senior vice president of clinical oncology and hematology at Roche’s Genentech unit, argued in his statement to panel members that the tumor shrinkage documented so far with Avastin “may predict overall survival” in the larger study that will start this year and end in 2014.

The FDA often follows the advice of its advisory panels, although it isn’t obligated to do so.

New Mechanism

Avastin was the first of a class of new treatments that work by blocking growth of blood vessels that feed tumor growth. It is approved to treat advanced colon, breast and lung cancers at a wholesale cost of $52,800 a year. Avastin was Genentech’s top-selling product in the U.S. in 2008, with revenue of $2.69 billion. Swiss parent Roche, which owned 56 percent of Genentech before last week’s deal, reported 2008 global sales of 5.21 billion Swiss francs ($4.82 billion).

Avastin’s brain cancer niche isn’t expected to add greatly to Roche’s bottom line, said Deutsche Bank analyst Mark Schoenebaum in an e-mail. He estimated $200 million in annual sales.

Roche rose 5.2 Swiss francs, or 3.4 percent, to 156.2 francs in Zurich trading before today’s vote. Genentech shares ceased trading March 26 on the New York Stock Exchange after its $46.8 billion takeover by Roche was completed.

Source : www.bloomberg.com

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