View all CSAC CME

Share a PER® activity with your colleagues or friends. Connect with the PER® social network.



Accreditation/ Credit Designation

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.

Cancer Summaries and Commentaries: Updates in Breast Cancer - PER Pulse™ Recap



Resources

PER Pulse™ Recap
Three PER Pulse™ Recaps summarize key data from the 2013 Annual Meeting, which was held May 31 - June 4, 2013, as well as faculty commentary on the impact of this data on community practice.



PER Pulse™ Recap

Cancer Summaries and Commentaries: Updates in Breast Cancer

1 of 3
PER Pulse™ Recap
The Evolving Utility of Dual HER2-Blockade

Medical Writer: Susan R. Peck, PhD

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 2013 Annual Meeting of the American Society of Clinical Oncology held in Chicago, IL, with a focus on abstracts concerning treatment strategies for patients with HER2-positive breast cancer, accompanied by commentary from Drs. Joyce O’Shaughnessy and Debu Tripathy. This first of 3 PER Pulse™ Recaps focuses on two phase III trials that investigated the use of dual HER2 blockade.

The phase III CALGB 40601 trial compared 16 weeks of neoadjuvant therapy with paclitaxel in combination with trastuzumab, lapatinib, or trastuzumab plus lapatinib to determine whether dual HER2 blockade could increase the pathologic complete response (pCR) rate compared with anti-HER2 monotherapy (abstract 500). Dual HER2 blockade was associated with a higher in-breast pCR rate (56%) versus the arms in which paclitaxel was combined with trastuzumab alone (46%) or with lapatinib alone (37%), although the differences between arms did not reach statistical significance. Rash and diarrhea were the most common grade 3/4 adverse events in the dual-blockade arm. No cases of congestive heart failure were reported in any of the treatment groups. Dr. O’Shaughnessy noted that these results were consistent with results from other neoadjuvant trials, such as NeoALTTO and NeoSPHERE, in which significant improvements in pCR rates were observed with dual-blockade approaches incorporating either lapatinib or pertuzumab respectively. Dr. Tripathy added that it will be important to see whether these increased pCR rates translate to improved disease-free survival, which is a more important endpoint for patients.

A second important abstract presented in Chicago concerned a retrospective subset analysis of the CLEOPATRA trial in patients with metastatic HER2-positive breast cancer that had previously been exposed to trastuzumab (abstract 600). The authors reported that the progression-free and overall survival benefits associated with first-line treatment with pertuzumab/trastuzumab/docetaxel compared with docetaxel/trastuzumab alone  were strikingly similar between the subset of patients with  previous exposure to trastuzumab and the overall study population. Prior trastuzumab therapy was also not a risk factor for the development of left ventricular systolic dysfunction. Drs. Tripathy and O’Shaughnessy both indicated that although the number of patients in the trastuzumab-exposed subset was small and confidence intervals were wide, they found these data reassuring.

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

 


2 of 3
PER Pulse™ Recap
Cardiac Toxicity With HER2-Directed Therapies

Medical Writer: Jennifer Klem, PhD

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 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, Illinois, with a focus on abstracts concerning treatment strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, accompanied by commentary from Drs. Joyce O’Shaughnessy and Debu Tripathy. This second of three PER Pulse™ Recaps focuses on two reports of cardiac toxicities in patients receiving HER2-directed therapies.

The first abstract (Abstract 525) reported cardiac toxicity results at a median follow-up of 8 years from theHERA) trial, which was designed to evaluate 1 or 2 years of adjuvant trastuzumab therapy in patients who had completed primary therapy for early-stage HER2-positive breast cancer. Previous results demonstrated that trastuzumab produced both disease-free and overall survival benefit but that the second year of trastuzumab therapy provided no additional advantage. Cardiac events among patients receiving trastuzumab steadily increased during trastuzumab therapy and plateaued at completion of therapy. A confirmed significant left ventricular ejection fraction (LVEF) decrease was identified in 4.1% of patients receiving 1 year of trastuzumab and in 7.2% of patients receiving 2 years of trastuzumab. Discontinuations due to a cardiac disorder occurred in 5.2% and 9.4% of patients, respectively. There were 5 cardiac deaths overall (observation arm, n=2; 2-year trastuzumab arm, n=3), and 0.8% of patients in both trastuzumab arms developed severe congestive heart failure (CHF). Of the patients experiencing severe CHF, acute recovery occurred in 71.4% of patients from the 1-year arm and in 84.6% from the 2-year arm. Recovery took a median of 9.7 months and 5.8 months, respectively, and was not maintained in all patients (40% from the 1-year arm and 36.4% from the 2-year arm experienced a subsequent LVEF decrease <50%). Overall, these results confirm the relatively low incidence of cardiac events with 1 year of adjuvant trastuzumab. Dr. O’Shaughnessy noted that the increase in cardiac toxicity observed with the second year of trastuzumab therapy suggests that cardiac monitoring should be continued beyond 1 year for those patients receiving ongoing trastuzumab for metastatic disease.

To evaluate the risk of cardiac toxicity associated with combined HER2 inhibition in patients with HER2-positive breast cancer, a meta-analysis of 6 randomized dual-HER2 blockade clinical trials was conducted and presented at 2013 ASCO (Abstract 624). The combined incidence of ≥ grade 3 CHF was 1.49% for the anti-HER2 monotherapy group and 0.88% for the dual-HER2 blockade group. The pooled odds ratio (OR) for CHF in patients receiving dual HER2 inhibition vs single-agent HER2 inhibition was 0.58 (95% CI, 0.26–1.27), which was not statistically significant (P = .17). The combined incidence of LVEF decline was 2.9% with anti-HER2 monotherapy and 3.1% with dual HER2 blockade, showing no significant difference between groups in the pooled OR (0.88; 95% CI, 0.53–1.48; P = .64). No significant ORs for cardiotoxic risk were observed in any of the subgroup analyses for treatment setting (ie, neoadjuvant vs metastatic) or specific HER2-directed therapies (eg, trastuzumab/pertuzumab vs trastuzumab). Both Drs. Tripathy and O’Shaughnessy indicated that these data provide reassurance that dual HER2 blockade does not appear to increase cardiac toxicity over single-agent HER2 blockade.

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

 


3 of 3
PER Pulse™ Recap
Therapies for HER2-Positive Advanced Disease

Medical Writer: Jennifer Klem, PhD

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 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, Illinois, with a focus on abstracts concerning treatment strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, accompanied by commentary from Drs. Joyce O’Shaughnessy and Debu Tripathy. This final of three PER Pulse™ Recaps focuses on two different approaches for treating patients with HER2-positive advanced disease.

The phase III BOLERO-3 trial added everolimus to weekly trastuzumab + vinorelbine in trastuzumab-resistant advanced breast cancer to determine whether the addition of the mTOR inhibitor could improve progression-free survival (PFS, primary endpoint) (Abstract 505). Median PFS was significantly prolonged by 1.2 months in the everolimus arm (7.0 vs 5.8 months; HR= 0.78; = .0067). Although exploratory analyses suggested that most subgroups favored the everolimus arm, PFS benefit appeared to be restricted to the hormone receptor (HR)–negative subgroup (compared with HR–positive subgroup) and the subgroup of patients without visceral involvement (compared with patients with visceral involvement). Finally, those patients who received prior (neo)adjuvant trastuzumab obtained greater PFS benefit from everolimus than did those who were trastuzumab naïve, as did younger patients compared with older patients. Overall survival data were immature, although there were fewer deaths on the everolimus arm (36.3% vs 41.1%). Dr. Tripathy called the 1.2-month improvement in median PFS “modest” but clarified that BOLERO-1 results in the frontline setting may add important information to the optimal use of everolimus. Dr. O’Shaughnessy added that, because of the subset analysis results, she would use this everolimus-containing regimen in HR–negative disease.

Morikawa and colleagues conducted a small study of 12 women with metastatic breast cancer who required surgical resection or biopsy of their brain metastases to examine the ability of lapatinib, capecitabine, and capecitabine’s metabolites to penetrate into the brain lesions of these patients (Abstract 514). After receiving a single dose of capecitabine preoperatively on the day of surgery (n=8) or daily lapatinib for up to 5 days (ending immediately prior to surgery; n=4), patients underwent craniotomy, during which multiple brain tissue samples were obtained from a single lesion. Drug concentrations were measured and drug penetrability was quantified by the ratio of drug concentration in the brain tissue and serum. All 8 patients treated with capecitabine had measurable levels of capecitabine and each of its metabolites in their brain metastases (mean, 0.27–1.81 µM). Median brain metastasis:serum ratios of capecitabine and its metabolite levels ranged from 0.06 to 5.26. All 4 patients treated with lapatinib had measurable levels of lapatinib in all tissue samples (mean, 1.0–63.6 µM), and these levels correlated positively with the number of preoperative lapatinib doses received. For the 3 patients receiving at least 3 preoperative doses of lapatinib, brain metastasis:serum ratios ranged from 5.3–9.8. Dr. O’Shaughnessy mentioned that she was impressed that these drugs were measured in the micromolar range, suggesting that those should be effective dosages in the brain and that lapatinib + capecitabine is a viable option for patients with HER2-positive brain metastases. Dr. Tripathy agreed, adding that more research is needed on this population because patients with HER2-positive brain metastases have a median survival of more than 3 years.

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


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.
 





Calendar of Events
SUNMONTUESWEDTHURSFRISAT
      1
2345678
9101112131415
16171819202122
23242526272829
3031
Filter By