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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.

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

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This activity is supported by an educational grant from Genentech.

OncoLogue: Breast Cancer Cases - PER Pulse™ Recaps

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PER Pulse™ Recap
Three PER Pulse™ Recaps highlighting key decision points from case presentations on breast cancer.



PER Pulse™ Recap

PER Pulse™ Recap
Medical Writer: Kelly McCoy Hayden, PhD


1 of 3
PER Pulse™ Recap:

OncoLogue: Breast Cancer Cases

OncoLogue is a dialogue among a panel of experts that reflects real-world clinical discussions. It allows participants to hear and see thought leaders discuss patient management and treatment issues, experience case-based learning, and digest evidence-based commentary regarding treatment decisions. To begin the OncoLogue: Breast Cancer Cases program, Dr. Debu Tripathy discussed patients with low- or high-risk, early-stage HER2-positive breast cancer with panelists Drs. Jasgit C. Sachdev and Joanne L. Blum. Highlights included:
  • Early-Stage, Low-Risk HER2-Positive Breast Cancer. Questions surround the management of patients with low-risk (tumor <1 cm, N0) HER2-positive breast cancer. The low level of evidence available leaves physicians weighing the risks of adjuvant chemotherapy plus trastuzumab with the small benefit that patients with a low risk of recurrence may derive. In a phase II study, low-risk HER2-positive patients who received 12 cycles of weekly paclitaxel plus trastuzumab (for 1 year), had a 3-year disease-free survival of approximately 99%. Another phase II trial reported similar results with docetaxel and cyclophosphamide plus trastuzumab (for 1 year). Thus, trastuzumab continues to play an important role in early-stage disease, but the chemotherapy backbone chosen may be flexible. However, the risk of cardiotoxicity should be considered.
     
  • Early-Stage, High-Risk HER2-Positive Breast Cancer. For higher-risk patients (≥1 cm tumor, ≥4 positive lymph nodes [LNs]) with early-stage, HER2-positive disease, the chemotherapy backbone is more relevant. The BCIRG 006 trial revealed that trastuzumab plus nonanthracycline chemotherapy regimens (docetaxel, carboplatin) elicited slightly worse, but not significantly different, outcomes than trastuzumab, doxorubicin, cyclophosphamide, and docetaxel. Therefore, the panelists tended to consider anthracycline-containing regimens for higher-risk patients, except those with significant cardiovascular risk factors. Combining multiple, adjuvant HER2-targeted agents may become an alternative option for this population, and results from ongoing trials are eagerly awaited.
     


2 of 3
PER Pulse™ Recap:

OncoLogue: Breast Cancer Cases

OncoLogue is a dialogue among a panel of experts that reflects real-world clinical discussions. It allows participants to hear and see thought leaders discuss patient management and treatment issues, experience case-based learning, and digest evidence-based commentary regarding treatment decisions. During this OncoLogue: Breast Cancer Cases program, Dr. Jasgit C. Sachdev discussed HER2-positive metastatic breast cancer (MBC) with panelists Drs. Debu Tripathy and Joanne L. Blum. Highlights included:
  • First-Line HER2-Positive MBC. The CLEOPATRA clinical trial established dual HER2 blockade with pertuzumab, trastuzumab, and docetaxel (or another taxane) as the first-line standard-of-care for HER2-positive MBC. In CLEOPATRA, this regimen significantly prolonged progression-free survival (PFS) and overall survival (OS) compared with trastuzumab and docetaxel, with no additional cardiac toxicity. However, higher rates of diarrhea, rash, and pruritus were reported. Ongoing clinical trials may provide alternative options, such as T-DM1 alone or with pertuzumab, for this population.
     
  • Trastuzumab-Experienced HER2-Positive MBC. The standard-of-care for trastuzumab-experienced patients remains less clear. Only about 10% of CLEOPATRA participants received adjuvant trastuzumab, all of whom had a disease-free interval (DFS) of ≥1 year. Whether dual HER2 blockade benefits patients with shorter DFS remains unknown. One option for such patients may be T-DM1, which was examined in the EMILIA trial in trastuzumab-experienced patients who progressed on metastatic treatment or within 6 months of receiving adjuvant treatment. In this trial, second-line T-DM1 significantly improved PFS and OS compared with lapatinib plus capecitabine. However, lapatinib plus capecitabine may still be a good option for some patients, such as those with central nervous system metastases. Studies have shown that these drugs may cross the blood-brain-barrier, but confirmatory data are awaited. Other investigational therapies that may help overcome resistance to HER2-targeted therapies include inhibitors of HSP90, IGF-1R, CDK, and the PI3K/mTOR pathway.


3 of 3
PER Pulse™ Recap:

OncoLogue: Breast Cancer Cases

OncoLogue is a dialogue among a panel of experts that reflects real-world clinical discussions. It allows participants to hear and see thought leaders discuss patient management and treatment issues, experience case-based learning, and digest evidence-based commentary regarding treatment decisions. During this OncoLogue: Breast Cancer Cases program, Dr. Joanne L. Blum discussed with panelists Drs. Debu Tripathy and Jasgit C. Sachdev therapeutic options for postmenopausal patients with estrogen receptor (ER)-positive metastatic breast cancer (MBC) that has progressed on a nonsteroidal aromatase inhibitor (NSAI):
  • Everolimus Plus Exemestane. Support for everolimus plus exemestane came from the BOLERO-2 trial, which enrolled patients previously treated with an NSAI, and potentially other endocrine therapies and/or chemotherapy. Compared with exemestane alone, everolimus plus exemestane doubled median progression-free survival in the total population, including patients >75 years. Although stomatitis is commonly reported with everolimus and exemestane, the panelists stressed that this adverse event (AE) is manageable with appropriate prophylaxis and proactive treatment. No predictive biomarkers that identify responders to everolimus plus exemestane have been validated, but are desired in light of the AEs associated with the combination.
     
  • Fulvestrant. Another option for these patients is fulvestrant. In the EFECT trial, adding fulvestrant (500 mg loading dose, 250 mg thereafter) to exemestane did not yield any additional benefit. However, the CONFIRM trial revealed that fulvestrant 500 mg significantly prolonged overall survival compared with fulvestrant 250 mg and was well tolerated, prompting many physicians to use fulvestrant after NSAI failure. Fulvestrant may therefore be a good option for patients who wish to avoid everolimus-associated AEs.
     
  • Investigational Therapies: Several therapies are under investigation for patients with ER-positive MBC, including inhibitors of CDK4/6, Src, and HDAC molecules. Results from clinical trials of these agents are eagerly awaited.
     


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™.

This activity is supported by an educational grant from Genentech.




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