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CHICAGO -- A breast cancer drug approved as initial therapy for advanced disease has also shown a marked benefit in second-line treatment, researchers reported here.

In a randomized phase III trial, palbociclib (Ibrance), combined with fulvestrant (Faslodex), more than doubled progression-free survival (PFS) compared with fulvestrant alone, according to , of the Royal Marsden Hospital in London, and colleagues.

The study was stopped after an interim analysis showed a marked improvement on PFS with the combination -- 9.2 months for palbociclib-fulvestrant versus 3.8 months for fulvestrant-placebo.

Patients taking the combination had higher rates of neutropenia and leukopenia, but symptomatic adverse events were similar between the arms, Turner told reporters at the American Society of Clinical Oncology annual meeting.

The data were published simultaneously in the .

Palbociclib, in combination with letrozole (Femara) was , on the basis of phase II trial, as initial endocrine-based therapy for postmenopausal women with metastatic breast cancer that is estrogen receptor-positive (ER) and human epidermal growth factor receptor 2-negative (HER2).

In the PALOMA3 trial, Turner and colleagues enrolled 521 pre- and postmenopausal women with metastatic cancer -- ER-positive and HER2-negative -- whose disease had progressed despite previous endocrine-based therapy.

It is, he said, the first phase III trial to examine the effect of palbociclib, which blocks key genes involved in cancer cell proliferation, the cyclin-dependent kinases 4 and 6.

Because the combination of palbociclib and fulvestrant appears to be able to overcome resistance to endocrine therapy, it is "likely to become a standard of care" in those women, Turner told 番茄社区.

Outside experts were also enthusiastic about the results.

"The future just got brighter for the large group of women with metastatic estrogen and/or progesterone receptor positive breast cancer," commented Charles Shapiro, MD, of the Tisch Cancer Institute at Mount Sinai Hospital in New York City.

The study "reminds me of the early work on trastuzumab (Herceptin) and chemotherapy -- striking results that provide meaningful clinical benefits to women without adding much in the way of side effects," he told 番茄社区.

But Shapiro cautioned that the study was stopped early because of the efficacy results, so that data on overall survival (OS) -- a key part of the trastuzumab work -- is not available.

Turner told 番茄社区 that researchers are still blinded as to the study drug assignments, so that OS data is being collected, but right now, "there have been very few deaths."

The primary endpoint of the study was PFS. The researchers randomly assigned participants to receive placebo plus fulvestrant, which selectively degrades estrogen receptors, or fulvestrant with palbociclib.

The hazard ratio for progression on the combination was 0.422 (95% CI 0.318-0.560, P<0.000001).

The most common adverse events seen were hematological side effects:

• Neutropenia of any grade: 79% in palbociclib-fulvestrant arm versus 3% in fulvestrant-placebo arm
• Leukopenia of any grade: 46% versus 4%
• Febrile neutropenia: 0.6% in each arm

Patients in the combination arm had a small increase in fatigue, alopecia, and infections, but the rates of serious adverse events were similar (9.6% in the combination arm and 14% in the placebo arm).

Among combination patients, 2.6% patients stopped treatment owing to adverse events versus 1.7% of placebo.

The advantage in PFS is "very encouraging," commented , of Massachusetts General Hospital cancer center in Boston.

But he told 番茄社区 that PFS in the study's fulvestrant-placebo arm was lower than has been previously seen, which needs to be considered when evaluating the study.

He added it's unclear how the results should fit into the "rapidly evolving landscape" of ER-positive breast cancer.

On the other hand, the "results are truly groundbreaking," commented , of the Geffen School of Medicine at the University of California Los Angeles, who was one of the early investigators of palbociclib.

The results are "excellent news for women suffering from this horrible disease," he told 番茄社区.

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