One arrow’s not enough

Leigh MacMillan, Ph.D.
Published: February, 2007

Think of targeted therapies as poison arrows piercing Achilles’ heel.

There’s validity to the idea that the new generation of drugs “take advantage of our improved knowledge of the biology of cancer to exploit weaknesses in its defenses,” says David Johnson, M.D., a lung cancer specialist at Vanderbilt-Ingram Cancer Center.

“But it’s incredibly simplistic to assume that every cancer will have only one such vulnerability. Most cancers are far, far, far more complex than that and will likely require not just one arrow into the heel of Achilles, but multiple arrows.”

Alan Sandler, M.D., of Vanderbilt-Ingram, and Roy Herbst M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, are taking just such an approach. They are studying the impact of two targeted agents, bevacizumab (Avastin), which blocks blood vessel formation, and erlotinib (Tarceva), which inhibits the epidermal growth factor receptor, in treating non-small cell lung cancer.

The early results, reported in 2006 at the American Society of Clinical Oncology meeting, suggest that the combination of the two targeted agents is nearly as effective in improving progression-free survival as Avastin combined with standard chemotherapy.

The median time to progression, the point at which half of the lung tumors began to grow again after treatment, was 4.4 months for Avastin plus Tarceva, compared to 4.8 months for Avastin plus chemotherapy, and 3.0 months for patients in the chemotherapy plus placebo group.

The study comes on the heels of a multi-center clinical trial led by Sandler that demonstrated that adding Avastin to the chemotherapy drugs paclitaxel (Taxol) and carboplatin in patients with advanced, non-squamous, non-small cell lung cancer improved median survival from 10.3 to 12.3 months.

“Two months may not sound like a lot,” Sandler says, “but that’s actually the first time in the front-line setting of non-small cell lung cancer that we’ve ever seen a targeted therapy improve survival, and it’s the first time in 10-plus years that we’ve seen any agent show an additional survival advantage in this cancer.”

Based on the work led by Sandler, Avastin was recently approved for use in advanced lung cancer. It’s now time to study the drug in earlier stage disease, Sandler says, and to continue testing rational combinations of targeted therapies. To do that, “we’re going to have to do a better job of enrolling patients in clinical trials,” he adds.

“The cure for cancer could be sitting on a shelf somewhere, but if we can’t study it, we’re never going to know.”

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