San Antonio Breast Cancer Symposium: More to Come on 2011 Practice Changers

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.