Tumor shrinkage is no small thing. It can be remarkably difficult to get hardy cancer cells to respond to treatment. And because most trials of experimental cancer drugs use only the sickest patients -- anything less would be unethical -- it's not surprising that few of them would survive for an extended time on any treatment. Plus, none of the newest cancer drugs has ever been suggested as a cure, only a delaying tactic against the disease.
Consequently, cancer experts at the meeting were encouraged by the results. "We are light years ahead" of the standard chemotherapy drugs now used to treat cancer, says Dr. George Demetri, a leading researcher from Dana-Farber Cancer Institute in Boston. "It will take time for all of this to come to fruition, but we have proved that if you pick the right target, you can affect the disease."
CAUSE FOR WORRY? Still, the Food & Drug Administration is increasingly looking for proof that novel agents will show a survival benefit before approving them. So, the lack of clear evidence of longer life in trials presented for new drugs from ImClone Systems, Protein Design Labs, and Genentech are likely to worry investors, even if cancer specialists are more sanguine.
First, the good news. Millennium Pharmaceuticals and AstraZeneca both reported unequivocably positive results on their leading cancer drugs. Millennium's MLN341, for the blood cancer multiple myeloma, blocks a protein common to many cancers called proteasome, which helps cells survive and divide. At ASCO, Millennium reported on a Phase II study of 78 myeloma patients with very advanced disease. The cancer was either stabilized or reduced in 77% of the patients, and 20% experienced almost complete remission.
So far, after six months of followup, the majority of patients have not relapsed. "We are very, very pleased," says Dr. Michael Kauffman, vice-president for medicine at Millennium.
SHRINKING TUMORS. Also very pleased is AstraZeneca, whose Iressa lung cancer drug was one of the ASCO meeting's stars. Iressa blocks a growth signal that encourages cancer cells to proliferate wildly. In a Phase II study of 216 patients with advanced forms of lung cancer who had already failed standard therapy, the tumors shrank by more than half in 10% of patients, while 36% experienced an improvement in symptoms. The responses showed up within 10 days of treatment, with virtually no side effects other than a skin rash.
Iressa targets the same cellular mechanism as ImClone's Erbitux, a cancer drug that the FDA refused to evaluate last December in part because of the controversial design of a colon cancer clinical trial. Erbitux was in the news again at ASCO, with a trial of the drug sponsored by the National Cancer Institute. The NCI trial of 123 patients with head and neck cancer followed a more traditional design: Half were treated with chemotherapy alone, the other half with chemo plus Erbitux.
Dr. Barbara Burtness of Yale University School of Medicine reported that the tumors shrank by more than half in 22.6% of the patients on Erbitux, compared with 9.3% of the chemo-only patients, considered a significant difference.
"BEST INDICATION." However, survival rates showed little improvement -- in part, said Burtness, because the chemo patients did better than expected. Erbitux patients lived an average of 7.2 months after treatment, while chemo patients lived 6.7 months. Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center in New York, a world renowned oncology researcher, says the trial still showed a clear benefit from Erbitux. "Tumor regression is the best indication we have" right now that these new agents are working, he says.
Protein Design's HuM195, for acute myeloid leukemia, ran into a similar problem. The drug, designed to improve the response to chemotherapy, produced complete remission in 29% of 94 patients and partial remission in an additional 7%. However, lead investigator Dr. Eric J. Feldman of Cornell University says the strong response "did not translate into improved survival." In spite of that, Feldman says the drug should be considered as standard therapy for patients who don't respond to chemo alone.
Genentech's Avastin also got a mixed response. The drug, which blocks a tumor cell's blood supply, prolonged the time before the cancer progressed by 2.5 times in patients in the late stages of kidney cancer -- an extremely deadly disease. Dr. James Yang of the NCI, the trial's lead investigator, noted that it caused tumors to shrink in only a few patients. Still, Yang says he's encouraged by the results and believes the drug should be useful in combination with chemotherapy.
That may not be the breakthrough news that investors were hoping for, but for patients, such incremental progress spells hope. By Catherine Arnst in Orlando