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Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

These PER Pulse™ Recaps are not approved for AMA PRA Category 1 Credit™.

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This activity is supported by an educational grant from Genentech.

Cancer Summaries and Commentaries: Advances in the Treatment of Metastatic Breast Cancer - PER Pulse™ Recap



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PER Pulse™ Recap
Three PER Pulse™ Recaps presenting key topics from the 2012 San Antonio Breast Cancer Symposium, which was held December 4-8, 2012.




PER Pulse™ Recap

PER Pulse™ Recap

Medical Writer: Susan R. Peck, PhD


1 of 3
Cancer Summaries and Commentaries: Advances in the Treatment of Metastatic Breast Cancer
Optimizing Endocrine Therapy and Chemotherapy for Advanced Breast Cancer

Cancer Summaries and Commentaries is an online CME publication that summarizes key presentations at international oncology meetings, with commentary from expert faculty to help put the new data into perspective. This edition of Cancer Summaries and Commentaries features highlights from the 35th Annual San Antonio Breast Cancer Symposium, held December 4-8, 2012, focusing on abstracts that impact the care of patients with metastatic breast cancer (MBC), accompanied by commentary from Drs. Joyce O’Shaughnessy and Hope Rugo. This first of 3 PER Pulse™ Recaps focuses on results from two large phase III trials concerning the optimal use of endocrine therapy and chemotherapy.

The randomized phase III Comparison of Faslodex In Recurrent or Metastatic Breast Cancer (CONFIRM) trial compared two dosages of fulvestrant (500 mg vs 250 mg) in postmenopausal patients with recurrent estrogen receptor-positive breast cancer following prior endocrine therapy (Abstract S1-4). Results from this final analysis, after 75% of deaths had occurred, verified that not only did the higher dosage of fulvestrant improve median progression-free survival (PFS), but there was also a significant improvement in overall survival (OS; 26.4 vs 22.3 months; P = .016). Further, there were no clinically relevant imbalances in the safety profile between the two dosages of fulvestrant. Dr. O’Shaughnessy noted that this OS advantage definitely confirms 500-mg dosing of fulvestrant as the standard of care. Dr. Rugo commented that the 4.1 month difference in OS was clinically meaningful for patients with hormone receptor-positive MBC, and that this study teaches us valuable lessons as we develop new drugs in the future.

The second selected abstract featured results from Study 301, which compared capecitabine versus eribulin in patients with advanced breast cancer who had previously received both an anthracycline and a taxane (Abstract S6-6). Results demonstrated that median PFS was nearly identical for the two treatments. While there was a slight trend toward improved OS with eribulin, this did not meet statistical significance in the intent-to-treat population (15.9 months vs 14.5 months; P =.056). However, prespecified exploratory analysis suggested that certain subgroups may benefit more from eribulin, including HER2-negative disease, endocrine receptor (ER)-negative disease, and triple-negative disease, warranting further investigation. Adverse events were consistent with known toxicity profiles. Dr. Rugo noted that this trial teaches us that in general, in unselected MBC, the order of agents is not important, but that each agent provides additional benefit. Both Dr. Rugo and Dr. O’Shaughessy agreed that selection of which agent to use first needs to be individualized for each patient, depending on specific clinical scenarios.

To read the full summaries and expert commentary for these and other selected abstracts, please click here to view this edition of Cancer Summaries and Commentaries.

Click here to download PDF version

 


2 of 3
Cancer Summaries and Commentaries: Advances in the Treatment of Metastatic Breast Cancer
Targeted Therapies for HER2+ Metastatic Breast Cancer

Cancer Summaries and Commentaries is an online CME publication that summarizes key presentations at international oncology meetings, with commentary from expert faculty to help put the new data into perspective. This edition of Cancer Summaries and Commentaries features highlights from the 35th Annual San Antonio Breast Cancer Symposium, held December 4-8, 2012, focusing on abstracts that impact the care of patients with metastatic breast cancer (MBC), accompanied by commentary from Drs. Joyce O’Shaughnessy and Hope Rugo. This second of 3 PER Pulse™ Recaps focuses on results with new targeted agents for HER2-positive MBC.

The global phase III CLEOPATRA trial was designed to assess the addition of pertuzumab to a trastuzumab/docetaxel backbone in patients with newly diagnosed HER2-positive, locally recurrent or MBC. The primary analysis demonstrated a striking improvement in both progression-free survival (PFS) and response rates, and led to FDA approval for this combination. A confirmatory analysis was recently conducted and demonstrated that patients receiving pertuzumab/trastuzumab with docetaxel lived significantly longer than those receiving trastuzumab/docetaxel alone (median overall survival [OS] not yet reached vs 37.6 months), translating to a statistically significant 34% relative reduction in the risk of death (HR = 0.66; 95% CI, 0.52-0.84; P =.0008) (Abstract P5-18-26). Both Drs. Rugo and O’Shaughnessy agreed that these data establish this triplet as a standard of care for the first-line treatment of HER2-positive MBC, and discussed related abstracts concerning the use of this triplet in elderly patients, as well as a phase II trial evaluating the alternate combination of pertuzumab/trastuzumab/paclitaxel.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate combining trastuzumab with microtubule inhibitor DM1, was approved by the FDA in February 2013 for patients with HER2-positive MBC who previously received trastuzumab and a taxane, separately or in combination. This approval was based on results from the EMILIA trial, which showed that T-DM1 significantly improved both PFS and OS compared with lapatinib plus capecitabine in this population. A meta-analysis of safety data from seven independent T-DM1 studies was conducted and presented in San Antonio (Abstract P5-18-06). T-DM1 appears to have a very tolerable safety profile; the most common grade ≥3 adverse events were thrombocytopenia (10%) and elevations of AST (4%), and in most cases dose modifications allowed patients to continue with the treatment. Dr. O’Shaughnessy noted that the thrombocytopenia was often a “paper toxicity”—clinical manifestations are rare, and platelet counts frequently recover quickly. Dr. Rugo indicated that T-DM1 was an exciting, well-tolerated new agent, and discussed some of her toxicity management strategies for transaminitis, thrombocytopenia, and hypokalemia.

To read the full summaries and expert commentary for these and other selected abstracts, please click here to view this edition of Cancer Summaries and Commentaries.

Click here to download PDF version

 


3 of 3
Cancer Summaries and Commentaries: Advances in the Treatment of Metastatic Breast Cancer
Enhancing Endocrine Therapy With Targeted Agents

Cancer Summaries and Commentaries is an online CME publication that summarizes key presentations at international oncology meetings, with commentary from expert faculty to help put the new data into perspective. This edition of Cancer Summaries and Commentaries features highlights from the 35th Annual San Antonio Breast Cancer Symposium, held December 4-8, 2012, focusing on abstracts that impact the care of patients with metastatic breast cancer (MBC), accompanied by commentary from Drs. Joyce O’Shaughnessy and Hope Rugo. This third of 3 PER Pulse™ Recaps focuses on strategies to increase the efficacy of endocrine therapy by targeting specific molecular pathways that are thought to contribute to resistance.

Initial results from the BOLERO-2 trial demonstrated that the addition of the mTOR inhibitor everolimus to exemestane significantly improved median progression-free survival (PFS) for postmenopausal patients with hormone receptor-positive breast cancer that had already progressed on a nonsteroidal aromatase inhibitor, and led to FDA approval. The current analysis, with a median follow-up of 18 months, confirmed the PFS advantage, and this benefit was observed for the combination therapy across all subgroups, including those with visceral metastases, without visceral metastases, and with bone-only disease (Abstract P06-04-02). The most common grade 3/4 adverse events (AEs) were stomatitis (8%), hyperglycemia (5%), and fatigue (4%); pneumonitis and interstitial lung disease were observed at low frequency, and generally were low grade and manageable by dose interruption and reduction. Dr. O’Shaughnessy thought the impact across patient subsets was interesting and clinically useful. Dr. Rugo commented that these results show a clinically significant PFS difference favoring the combination that allows patients to stay on oral therapy longer. Both agreed they are awaiting the mature overall survival results with interest, noting a trend in favor of the combination.

One of the abstracts emerging from San Antonio that gained the most attention and excitement was the presentation of data from a randomized phase II trial, TRIO-18. This study investigated the addition of PD-0332991 (palbociclib), a member of a novel class of compounds that inhibits CDK 4/6, to letrozole as first-line endocrine therapy for postmenopausal patients with estrogen receptor-positive, HER2-negative advanced/MBC. Results showed a dramatic improvement in median PFS with the combination compared with letrozole alone (from 7.5 to 26.1 months). The combination was generally tolerable; hematologic abnormalities were the most frequent AEs and could usually be managed with dose reductions or delays. Based on these promising results, the combination is now being investigated in a phase III trial. Both Drs. Rugo and O’Shaughnessy expressed enthusiasm for the potential of this new combination and the planned phase III trial, although Dr. Rugo cautioned that the current results are not conclusive, and that we have seen sobering results before with agents that have shown promise in the phase II setting.

To read the full summaries and expert commentary for these and other selected abstracts, please click here to view this edition of Cancer Summaries and Commentaries.

Click here to download PDF version


 

Physicians’ Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

This activity is not approved for AMA PRA Category 1 Credit™.

Supported by educational grant from Genentech.




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