Now or Later?

Patients taking Alimta (pemetrexed) as a maintenance therapy for advanced non-squamous lung cancer lived a median of five months longer than patients taking a placebo, according to a randomized study reported at last year’s American Society of Clinical Oncology meeting.

The results for Alimta, an intravenous medication, were one in a series of maintenance treatment studies presented at the meeting. Maintenance therapy actually reflects various approaches to prescribing drugs like Alimta, either immediately after chemotherapy ends, or after giving patients with advanced cancer a treatment break, says Nasser Hanna, MD, an associate professor at Indiana University Melvin and Bren Simon Cancer Center, who gave a presentation about maintenance therapy at ASCO. Second-line therapy typically refers to treatment given after the patient’s cancer progresses on initial therapy, whereas maintenance therapy is given after the cancer responds to first-line treatment.

At the ASCO meeting, researchers presented findings showing the median overall survival difference with Alimta was three months, 13.4 months versus 10.6 months for patients taking a placebo. But an analysis of a subset of 482 patients diagnosed with non-squamous lung cancer showed they were the greatest beneficiaries. Their median survival was 15.5 months versus 10.3 months in the placebo group. “That’s the eye-popping part,” Hanna says. “That would be a survival gain that we are really not used to seeing [in lung cancer].”

FDA officials cited those results last July when they approved Alimta for maintenance treatment in patients with advanced non-squamous disease whose cancer hasn’t progressed following chemotherapy.

Research involving Tarceva (erlotinib) as maintenance therapy following chemotherapy was also presented at ASCO showing the EGFR inhibitor only slightly increased progression-free survival. In one study, progression-free survival reached a median of 12.3 weeks in patients on Tarceva, compared with 11.1 weeks for those taking placebo. Patients in the Tarceva group lived only slightly longer than patients in the placebo group, with median overall survival reaching 12 months and 11 months, respectively.

In another trial, progression-free survival was slightly longer with a maintenance therapy combo of Avastin (bevacizumab) plus Tarceva, reaching 4.8 months, compared with 3.7 months for Avastin maintenance therapy alone. Patients in both arms received initial treatment with Avastin and chemotherapy.

Last December, an advisory panel to the FDA recommended against approval of Tarceva for maintenance. For lung cancer, the drug is only approved for use in advanced disease once chemotherapy fails.

These studies to date, as well as the Alimta analysis, haven’t provided a good sense of when maintenance treatment should begin, says Hanna, who worries about overtreating patients whose cancer might not advance right away and who could enjoy a respite from treatment-related side effects. In the Alimta study, serious side effects, including fatigue and neutropenia (a worrisome decrease in white blood cells), were more common in the Alimta group.

Ultimately, the weighing of risks and benefits is a personal decision between patient and physician, Hanna says. “Some patients will absolutely want breaks. Some patients will absolutely not want a break. It can really not be a one-size-fits-all.”