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Palbociclib doubled the average amount of progression-free survival (PFS) time among patients with advanced breast cancer. But in the first detailed glimpse of its impact on overall survival (OS) - a key feature to the future prospects of this flagship program - the therapy has failed to demonstrate a statistically significant improvement in extending patients' lives after an initial assessment. Palbociclib is on of the cyclin-dependent kinase inhibitors.

Patients with hormone receptor-positive metastatic breast cancer enjoyed a median PFS rate of 20.2 months when taking a combination of palbociclib and the antiestrogen drug Femara (letrozole), compared to 10.2 months for letrozole alone, according to researchers presenting the latest data at the American Association for Cancer Research (AACR)meeting in San Diego. The OS rate, though, was 37.5 months for the combo versus 33.3 months for the solo therapy. That was an improvement, but not a big enough one to qualify as significant enough to meet the secondary endpoint.

Investigators were quick to note that there haven't been enough patient deaths in the study to firm up the OS numbers, happy at this stage to point to a trend in the drug's favor. But investors were left feeling somewhat deflated over the shortfall on OS, especially after seeing signs of a dramatic improvement in PFS earlier on. At the interim point, patients taking palbociclib saw a delay in disease progression of 26.1 months, compared to only 7.5 months in the control arm.

Financial analysts had expected the PFS rate over the letrozole arm to balance out a bit in the follow-up. And they expect the results are sufficient for a regulatory application soon, which is what investors have been gambling on. Pfizer (the drug's manufacturer), though, hasn't come right out and said whether they're going for an early approval.

Palbociclib is a CDK-4/6 inhibitor. And it's not alone. Last December, Novartis pushed its rival program for LEE011 into Phase III, setting up a showdown over a market that could deliver billions in potential revenue. Both therapies target a pair of cyclin dependent kinases that play a role in cancer. Eli Lilly also has a contender in the pipeline, LY2835219. But the pharma giant is well behind the leaders in this race, and Lilly suffers from a reputation for carefully regimented development programs that often lag well behind those of rivals.

Lilly's investigators reported at AACR that of the 47 patients with metastatic breast cancer in the study, 9, or 19%, had a partial response while 24, 51%, had stable disease. "Disease progressed despite treatment in 11 patients," according to a release from Lilly. "All of the nine patients who had a partial response, and 20 of the 24 patients who had stable disease, had HR-positive disease, which meant that the partial response and stable disease rates for patients with HR-positive disease were 25 percent and 55 percent, respectively."

Schoenebaum takes a positive view on Lilly's come-from-behind position in the race for an approval. "Overall, these data seem to indicate that (Lilly's) drug is clearly active," he wrote. "Whether it's actually MORE active than Pfizer's palbociclib remains an open question as you must be very careful when comparing across different trials with small patient numbers. As a reminder, Lilly has argued that their drug might work better because it can be dosed continuously (vs palbociclib's 3 weeks on; 1 week off regimen) due to less severe neutropenia. Lilly plans on announcing next steps later in the first half of 2014 - we believe it's possible that a phase 3 could begin by year 2014's end or in early 2015. There is very little, if anything, in Lilly consensus estimates for this drug - so in theory, at least, it represents all upside."

The view from Pfizer's investigators remained upbeat, despite the setback on OS rates.

"This is an exciting data set that shows a major clinical benefit for patients who have hormone receptor-positive, metastatic breast cancer," said UCLA Professor Dennis Slamon. "The potential impact of this study could be huge. We are doing further Phase III work with the drug, but the current data are as exciting as the initial studies we were involved in when testing Herceptin for HER2-positive breast cancers."

Source: FierceBiotech