ASCO Confab: Who's Grabbing the Spotlight?

Genentech's been the star of the cancer conference, but Pfizer and Celgene also make headlines.
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Editor's note: This article compiles some of the major stories that emerged over the weekend at the annual meeting of the American Society of Clinical Oncology in Orlando, Fla. The following items were reported by's

Althea Chang and first appeared in the Columnist Conversation on


from May 14-16. Althea will continue to monitor events from Florida until the conclusion of the conference.

ASCO Update



Avastin improved lung cancer survival when added to standard combination chemotherapy, according to research presented at this year's meeting of the American Society of Clinical Oncology. Avastin delayed disease progression and allowed for longer survival of non-small cell lung cancer patients, according to the research.

In a phase III trial comparing the use of paclitaxel and carboplatin, with and without Avastin, patients who received Avastin experienced cancer progression two months later and lived more than two months longer than patients who did not.

The most common side effects seen in the trial were low infection-fighting white blood cell count, blood clots and bleeding. The most significant side effect, was life threatening and even fatal bleeding from the lungs, researchers reported. This side effect occurred in 1.2% of those on Avastin, compared with none on standard chemotherapy alone. The condition was observed in 9% of patients in a previous phase II trial.

Avastin is currently approved for colon cancer, but it's being studied as a potential treatment for other types of cancers. Avastin is a part of a class of cancer drugs that stop vascular endothelial growth factor (or VEGF), a cellular substance that stimulates new blood vessel formation.

Novartis/Schering Data at ASCO

An experimental VEGF inhibitor, PTK/ZK, or vatalanib, failed to show a significant improvement in progression-free survival of colorectal cancer patients, according to interim trial results presented at the meeting of the American Society of Clinical Oncology.

An interim analysis of phase III data of the drug, which was developed by


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, failed to show a statistically significant survival benefit, researchers said. In a trial involving 1,168 patients on Folfox chemotherapy, patients who were additionally treated with PTK/ZK didn't see a meaningful improvement in survival without disease progression. Folfox, a combination therapy, is the most common treatment for colorectal cancer.

Side effects of PTK/ZK included hypertension and thromboembolic events. Researchers said PTK/ZK didn't increase bleeding or bowel perforation when compared with a placebo. The trial is ongoing and final results are expected in the second half of 2006. In its first quarter earnings release last month, Novartis reaffirmed its plans to submit PTK/ZK for regulatory approval in 2007.

On the positive side, the study did show that 40% of patients with a high level of LHD, an enzyme that suggests the presence of tissue damage, did show significantly improved progression-free survival.

In a press release, Novartis added that patients who received the PTK/ZK-Folfox combination had a 17% reduction in risk of disease progression, compared with Folfox alone when assessed by the patients' physicians. Assessment by central review showed a 12% reduction in risk of disease progression, however, the difference did not achieve statistical significance.

Positive Data from Bayer, Onyx

Trial findings from




Onyx Pharmaceuticals


for the experimental drug sorafenib confirmed interim phase III results in progression-free survival of advanced renal cell carcinoma, according to data discussed at the annual meeting of the American Society of Clinical Oncology.

As assessed by an independent review, progression-free survival was doubled to a median value of 24 weeks (167 days) in patients receiving sorafenib, vs. 12 weeks (84 days) for patients receiving the placebo.

Kidney cancer is resistant to most cancer drugs, but Sorafenib stopped or shrank growing tumors in trials comparing the drug and a placebo, researchers said. Sorafenib is running neck and neck in the race to Food and Drug Administration approval with


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experimental drug Sutent. Some analysts expect Sutent to come to market under another indication in this year's fourth quarter, then gain label expansion to include kidney cancer in early 2006.

Pfizer inherited Sutent after its 2002 acquisition of Pharmacia. The product is also in trials for stomach cancer.

Based on the positive interim results, the companies plan to file for FDA approval of the treatment.

Tarceva Sound in Pancreatic Cancer Trial

Tarceva, the Genetech and

OSI Pharmaceuticals


drug, lets advanced pancreatic cancer patients live longer, according to trial data presented at the ASCO meeting.

The addition of Tarceva to gemcitabine chemotherapy improved overall survival by 23.5% compared with patients receiving the chemotherapy alone. The phase III safety and efficacy trials involved 569 patients, spanning 17 countries and 140 study centers.

Median survival for patients receiving Tarceva plus chemotherapy was 6.4 months vs 5.9 months for those who took the gemcitabine and a placebo.

Sutent Side Effect

Pfizer's experimental drug Sutent, formerly SU11248, caused hyperthyroidism in a subset of its phase I/II trial of patients with gastrointestinal stromal tumors, researchers said at ASCO on Sunday.

Hyperthyroidism is characterized by abnormally high levels of thyroid-stimulating hormone, and was manageable with additional drug therapy. In a dose escalation study of patients with metastatic gastroinstestinal stromal tumors, who had unsuccessful prior treatment with Imatinib, 40% of patients experienced thyroid dysfunction after using Sutent.

The side effect didn't require an interruption or adjustment of the Sutent dosage, researchers say, but the results "warrant further investigation."

More on Avastin

The incidence of life-threatening bleeding associated with Genentech's drug was lower in the most recent phase III lung cancer trial than in a previous study.

Leading up to the ASCO annual meeting, analysts and investors were concerned about the rate of hemoptysis, a potentially fatal bleeding of the lungs, that occurred as a side effect in 9% of patients in a phase II Avastin trial, but only 1.2% of patients in the phase III trial.

However, according to Dr. Alan Sandler, the lead author of the phase III study, the latest trial didn't include squamous cell lung cancer patients.

Note that squamous cell lung cancer patients made up a majority of those who experienced hemoptysis in the phase II Avastin trial. Also, the recent study excluded patients who had previously experienced hemoptysis, but the phase II trial did not.

Rituxan and AIDS-related lymphoma

Biogen Idec's

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Rituxan improved disease control and increased overall survival in patients with AIDS-related lymphoma, according to data released at the ASCO meeting Sunday. However, the drug increased the risk of death from infection.

In one study, Rituxan was added to a combination drug therapy called CHOP, consisting of cyclophosphamide, doxorubicin, vincristine and prednisone, a cocktail of anticancer, antibiotic and anti-inflammatory drugs. Treatment-related infection occurred in 14% of patients who took Rituxan, while infections occurred in only 2% of those on CHOP alone.

Rituxan is co-promoted by Genentech, the star of this year's ASCO meeting.

Multitargeted Therapies

Genentech's Avastin and Tarceva were the subject of several special sessions at the American Society of Clinical Oncology annual meeting in Orlando, Fla., but according to doctors here, this is only the beginning for a class of multitargeted therapeutic drugs.

The best combinations and the safest, most effective dosages of drugs still need to be found, said Dr. Roy Herbst of the MD Anderson Cancer Center in Houston. Tarceva was co-developed by OSI Pharmaceuticals.

Tests to determine which patients will benefit most from such drugs also need to be developed. So far, Tarceva and


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Iressa appear to be most effective in females, nonsmokers, East Asians and those with adenocarcinomas, says Dr. Daniel Haber of the Massachusetts General Hospital Cancer Center. Thus, doctors should be able to predict who might be resistant to the drugs and possibly develop ways to circumvent that resistance.

Celgene's Revlimid

According to interim phase III trial data released at ASCO, 26.5% of patients taking


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Revlimid plus dexamethasone saw a complete response to the treatment compared with 4.1% who took a placebo plus dexamethasone.

In a trial involving 354 heavily pretreated relapsed or refractory multiple myeloma patients, about half received Revlimid plus dexamethasone and half dexamethasone alone. The median patient age was 64 years in the Revlimid plus dexamethasone arm vs. 62 in the dexamethasone-alone arm of the trial.

An independent monitoring committee reviewed the planned interim analysis of clinical data and determined that the U.S. phase III trial vastly exceeded the expected efficacy. These data confirmed positive trial results previously reported, and studies are ongoing.

ImClone Medical Chief Speaks



chief medical officer, Dr. Eric Rowinsky, says cancer researchers are working to "develop selective agents to thwart highly specific molecular aberrations" that target specific areas of the complex networks involved in tumor growth.

"It's na?ve to think that any one manipulation by a single agent will produce robust results," Rowinsky says, "except when targets are highly aberrant."

For example, mutations in the epidermal growth factor receptor pathway are high in people of Japanese ancestry, so EGFR-targeting drugs are more effective for that population. However, there is no readily identifiable "driving" aberration that causes and accelerates tumor growth. It's important to find the most effective combinations of cancer drugs, Rowinsky says, but this goal has been a "bottleneck in cancer research."

Mesothelioma Trials Disappoint

Genentech's Avastin and AstraZeneca's Iressa produced disappointing results in mesothelioma trials.

Mesothelioma is a cancer of the protective layer that covers the internal organs. The rare disease occurs mostly in patients who have been exposed to asbestos particles.

In a small phase II study presented at the American Society of Clinical Oncology annual meeting in Orlando, Fla., patients taking Avastin in addition to chemotherapy drugs gemcitabine and cisplatin survived without disease progression for 6.4 months on average. The goal of the study was to achieve progression-free survival of seven months with the addition of Avastin, compared with four months for patients on gemcitabine and cisplatin alone.

According to Dr. Hedy Lee Kindler, director of the mesothelioma program at the University of Chicago, mesothelioma patients have the highest level of vascular endothelial growth factor levels of all solid tumor types. Kindler presented data on the Avastin trial.

Meanwhile, Dr. Ramaswamy Govindan of Washington University, says higher VEGF levels indicated a lower chance of survival. Govindan, who presented data on mesothelioma trials involving AstraZeneca's Iressa, said use of that drug also produced disappointing results. Mesothelioma affects about 2,500 people in the U.S. each year, researchers say.

Tarceva Falls Short

Genentech's Tarceva showed lower-than-expected tumor-fighting activity in patients with recurring or refractory metastatic breast cancer, according to researchers at ASCO.

The results of a phase II trial of the efficacy and tolerability of the drug in addition to gemcitabine chemotherapy fell short of expectations based on previous studies. Of 58 patients enrolled in the trial, only 10 saw a partial response characterized by a 50% or more reduction in tumor size after taking the drug. Tarceva had only a modest effectiveness when used alone for metastatic breast cancer, researchers added.

Avastin and Blood Vessel Blockage

Adding Genentech's Avastin to a standard chemotherapy regimen doubles the chance of blood vessel blockage known as an arterial thromboembolism, according to data from a study of 1,745 patients with metastatic colorectal, breast or non-small-cell lung cancer.

Researchers identified a history of the embolisms and an age of more than 65 as independent risk factors of the cancer drug's serious side effect. Avastin is currently approved for the treatment of colorectal cancer.