New combination therapy for breast cancer one step closer to approval

17 Nov 2016

Researchers studied the effects of adding palbociclib to letrozole for the treatment of estrogen receptor positive (ER+), HER2-negative (HER2-) advanced breast cancer. The results showed an increase in progression-free survival from 14.5 to over 25 months (compared to letrozole alone).

Palbociclib and clinical trials

The “breakthrough” drug palbociclib targets a key family of proteins to prevent cell growth in cancer, report investigators. The new study treated women with estrogen receptor positive (ER+), HER2-negative (HER2-) advanced breast cancer with a combination of palbociclib and standard anti-estrogen therapy letrozole.

Building on earlier clinical trials, UCLA researchers have confirmed that the "breakthrough" drug palbociclib when used in combination with the traditional hormonal therapy letrozole delays progression of advanced breast cancer significantly and without the harsh side effects seen in some women prescribed letrozole alone.

Approval history

The study, published online in the New England Journal of Medicine, is the phase 3 study. It follows the phase 1 and phase 2 clinical trials that led to the U.S. Food and Drug Administration approval of palbociclib in early 2015. Palbociclib was also approved in Europe for the first time in November based on these results. In 2013, after women in a clinical study led by UCLA researchers showed a dramatic improvement, the FDA granted palbociclib "breakthrough therapy" status, allowing it to be fast-tracked for approval.

The drug combination is the first and only treatment for women with estrogen-receptor-positive breast cancer to show such significant results in a randomized phase 3 trial. Dr. Richard Finn and Dr. Dennis Slamon of the UCLA Jonsson Comprehensive Cancer Center led the laboratory studies and previous trials and are co-authors of the study.

"These results are a truly meaningful advancement for women in this patient population," said Finn, who is also an associate professor of medicine in the David Geffen School of Medicine at UCLA. "The results of the phase 3 study will support the full approval of palbociclib in the United States and around the world."

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Study details: preventing tumor growth

Palbociclib is known as the first new drug that in combination with hormonal therapy has proven to be very effective in post-menopausal women with estrogen receptor-positive breast cancer. The ER+/HER2- subgroup represents the largest proportion of breast cancer cases and is traditionally treated with therapies, like tamoxifen or letrozole, that target the hormone receptor pathway. Palbociclib prevents cells from dividing by targeting a key family of proteins (CDK4/6) responsible for cell growth.

Led by Finn and Slamon, an international team of investigators from 17 countries analyzed 666 women with advanced ER+/HER2- breast cancer. The people were treated with a combination of palbociclib and letrozole and had not received prior systemic therapy for their cancer. The results of the new study confirmed the previous findings of the multi-year phase 1 and phase 2 trials, which showed a significant increase in the time it took the cancer to progress compared to letrozole alone.

The phase 2 trial also demonstrated that survival without side effects nearly doubled (20.2 months for women who received palbociclib plus letrozole compared to 10.2 months in patients who received letrozole alone) representing a 42% reduction in the risk of disease progression. The new phase 3 trial further confirmed these findings.

Researchers: very well tolerated combination, with less side-effects

"The results from both studies are really remarkable for the degree of benefit they provide in slowing the growth of estrogen-receptor positive breast cancer," said Slamon, director of the Revlon/UCLA Women's Cancer Research Program and director of clinical and translational research at the Jonsson Cancer Center. "The drug combination is very well tolerated and without the side effects of traditional chemotherapy, such as infections, nausea and significant hair loss."

Palbociclib is the first CDK 4/6 treatment to be approved for cancer treatment and provides proof of concept that targeting this pathway is important for the treatment of women with ER+ breast cancer. The researchers said the phase 3 findings will open the door to further studies in breast cancer and other diseases.

 

Source: Science Daily

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