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– The inability of researchers to find a biomarker that could flag a subgroup of breast cancer patients with increased responsiveness to ribociclib plus an aromatase inhibitor was “somewhat disappointing,” Philippe Bedard, MD, said at a breast cancer conference sponsored by the European Society for Medical Oncology.

Many patients who are candidates for this combination treatment, approved by the Food and Drug Administration in March 2017 for postmenopausal women with advanced breast cancer that is hormone receptor positive and HER2 negative, could also do just as well on an aromatase inhibitor alone, said Dr. Bedard, of the Princess Margaret Cancer Centre in Toronto.

Mitchel L. Zoler/Frontline Medical News
Dr. Philippe Bedard
“Being able to identify which patients would do well or not do well on the combination could allow us to tailor our treatments to avoid additional toxicity from ribociclib and avoid frequent monitoring of blood counts, as well as avoid additional drug cost,” said Dr. Bedard, designated discussant for the biomarker analysis reported at the meeting. Monotherapy with an aromatase inhibitor such as letrozole (Femara) might also be a more attractive option for women who are minimally symptomatic with an indolent tumor, he noted.

“The only validated marker for response to a cyclin-dependent kinase 4/6 inhibitor [such as ribociclib] is hormone receptor positivity. The bottom line is that you can’t target to a more specific subgroup with a biomarker,” Dr. Bedard said in an interview.

Mitchel L. Zoler/Frontline Medical News
Dr. Fabrice André
The new biomarker analysis of treatment with ribociclib plus letrozole came from an exploratory analysis of data collected in the MONALEESA-2 (Mammary Oncology Assessment of LEE011’s [Ribociclib’s] Efficacy and Safety) trial, which randomized 668 women with recurrent or metastatic hormone receptor positive, HER2 negative breast cancer who had not previously received systemic treatment to either ribociclib plus letrozole or placebo plus letrozole. During 18-month follow-up, progression-free survival on the dual therapy had a hazard ratio of 0.56, compared with that on letrozole alone (P = .00000329 for superiority), the finding that led to FDA approval in March 2017 for using ribociclib (Kisqali) plus letrozole in this patient population (New Engl J Med. 2017 Nov 3;375[18]:1738-48).*

The researchers who ran the study collected tumor specimens at baseline from all participants, and Fabrice André, MD reported results from analyses run for seven different biomarkers. The analysis looked at protein levels for three biomarkers – Rb, Ki67, and p16 – in 479, 463, and 405 patients respectively; messenger RNA levels for CCND1, CDKN2A, and ESR1 in 386 patients; and DNA mutational status for the PIKC3A gene in 573 patients. In all seven cases, responsiveness to ribociclib was roughly similar regardless of protein or RNA expression levels or the type of PIKC3A (wild or mutated) the tumor carried, reported Dr. André of the Gustave Roussy Cancer Institute in Villejuif, France. Additional biomarker studies on the MONALEESA-2 specimens are ongoing, he said.

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– The inability of researchers to find a biomarker that could flag a subgroup of breast cancer patients with increased responsiveness to ribociclib plus an aromatase inhibitor was “somewhat disappointing,” Philippe Bedard, MD, said at a breast cancer conference sponsored by the European Society for Medical Oncology.

Many patients who are candidates for this combination treatment, approved by the Food and Drug Administration in March 2017 for postmenopausal women with advanced breast cancer that is hormone receptor positive and HER2 negative, could also do just as well on an aromatase inhibitor alone, said Dr. Bedard, of the Princess Margaret Cancer Centre in Toronto.

Mitchel L. Zoler/Frontline Medical News
Dr. Philippe Bedard
“Being able to identify which patients would do well or not do well on the combination could allow us to tailor our treatments to avoid additional toxicity from ribociclib and avoid frequent monitoring of blood counts, as well as avoid additional drug cost,” said Dr. Bedard, designated discussant for the biomarker analysis reported at the meeting. Monotherapy with an aromatase inhibitor such as letrozole (Femara) might also be a more attractive option for women who are minimally symptomatic with an indolent tumor, he noted.

“The only validated marker for response to a cyclin-dependent kinase 4/6 inhibitor [such as ribociclib] is hormone receptor positivity. The bottom line is that you can’t target to a more specific subgroup with a biomarker,” Dr. Bedard said in an interview.

Mitchel L. Zoler/Frontline Medical News
Dr. Fabrice André
The new biomarker analysis of treatment with ribociclib plus letrozole came from an exploratory analysis of data collected in the MONALEESA-2 (Mammary Oncology Assessment of LEE011’s [Ribociclib’s] Efficacy and Safety) trial, which randomized 668 women with recurrent or metastatic hormone receptor positive, HER2 negative breast cancer who had not previously received systemic treatment to either ribociclib plus letrozole or placebo plus letrozole. During 18-month follow-up, progression-free survival on the dual therapy had a hazard ratio of 0.56, compared with that on letrozole alone (P = .00000329 for superiority), the finding that led to FDA approval in March 2017 for using ribociclib (Kisqali) plus letrozole in this patient population (New Engl J Med. 2017 Nov 3;375[18]:1738-48).*

The researchers who ran the study collected tumor specimens at baseline from all participants, and Fabrice André, MD reported results from analyses run for seven different biomarkers. The analysis looked at protein levels for three biomarkers – Rb, Ki67, and p16 – in 479, 463, and 405 patients respectively; messenger RNA levels for CCND1, CDKN2A, and ESR1 in 386 patients; and DNA mutational status for the PIKC3A gene in 573 patients. In all seven cases, responsiveness to ribociclib was roughly similar regardless of protein or RNA expression levels or the type of PIKC3A (wild or mutated) the tumor carried, reported Dr. André of the Gustave Roussy Cancer Institute in Villejuif, France. Additional biomarker studies on the MONALEESA-2 specimens are ongoing, he said.

 

– The inability of researchers to find a biomarker that could flag a subgroup of breast cancer patients with increased responsiveness to ribociclib plus an aromatase inhibitor was “somewhat disappointing,” Philippe Bedard, MD, said at a breast cancer conference sponsored by the European Society for Medical Oncology.

Many patients who are candidates for this combination treatment, approved by the Food and Drug Administration in March 2017 for postmenopausal women with advanced breast cancer that is hormone receptor positive and HER2 negative, could also do just as well on an aromatase inhibitor alone, said Dr. Bedard, of the Princess Margaret Cancer Centre in Toronto.

Mitchel L. Zoler/Frontline Medical News
Dr. Philippe Bedard
“Being able to identify which patients would do well or not do well on the combination could allow us to tailor our treatments to avoid additional toxicity from ribociclib and avoid frequent monitoring of blood counts, as well as avoid additional drug cost,” said Dr. Bedard, designated discussant for the biomarker analysis reported at the meeting. Monotherapy with an aromatase inhibitor such as letrozole (Femara) might also be a more attractive option for women who are minimally symptomatic with an indolent tumor, he noted.

“The only validated marker for response to a cyclin-dependent kinase 4/6 inhibitor [such as ribociclib] is hormone receptor positivity. The bottom line is that you can’t target to a more specific subgroup with a biomarker,” Dr. Bedard said in an interview.

Mitchel L. Zoler/Frontline Medical News
Dr. Fabrice André
The new biomarker analysis of treatment with ribociclib plus letrozole came from an exploratory analysis of data collected in the MONALEESA-2 (Mammary Oncology Assessment of LEE011’s [Ribociclib’s] Efficacy and Safety) trial, which randomized 668 women with recurrent or metastatic hormone receptor positive, HER2 negative breast cancer who had not previously received systemic treatment to either ribociclib plus letrozole or placebo plus letrozole. During 18-month follow-up, progression-free survival on the dual therapy had a hazard ratio of 0.56, compared with that on letrozole alone (P = .00000329 for superiority), the finding that led to FDA approval in March 2017 for using ribociclib (Kisqali) plus letrozole in this patient population (New Engl J Med. 2017 Nov 3;375[18]:1738-48).*

The researchers who ran the study collected tumor specimens at baseline from all participants, and Fabrice André, MD reported results from analyses run for seven different biomarkers. The analysis looked at protein levels for three biomarkers – Rb, Ki67, and p16 – in 479, 463, and 405 patients respectively; messenger RNA levels for CCND1, CDKN2A, and ESR1 in 386 patients; and DNA mutational status for the PIKC3A gene in 573 patients. In all seven cases, responsiveness to ribociclib was roughly similar regardless of protein or RNA expression levels or the type of PIKC3A (wild or mutated) the tumor carried, reported Dr. André of the Gustave Roussy Cancer Institute in Villejuif, France. Additional biomarker studies on the MONALEESA-2 specimens are ongoing, he said.

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Key clinical point: An exploratory analysis for biomarker links to ribociclib responsiveness in the MONALEESA-2 trial failed to find any biomarker that flagged better or worse clinical responses to the drug.

Major finding: Hazard ratio benefits from ribociclib plus letrozole, compared with letrozole alone, were similar regardless of the levels of seven biomarkers.

Data source: Exploratory analysis of tumor specimens collected from 668 patients with breast cancer enrolled in the MONALEESA-2 study.

Disclosures: MONALEESA-2 was sponsored by Novartis, the company that markets ribociclib (Kisqali). Dr. Bedard has received honoraria from Novartis, Pfizer, Roche, and Sanofi, and he has received research funding from Novartis and several other companies. Dr. André has received research funding from Novartis, AstraZeneca, Lilly, and Pfizer.