Seven Studies at SABCS Make Dr. Jame Abraham's List of 'Practice-Changing' Talks


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Jame Abraham, MD

From December 10 to 14, the American Association for Cancer Research, the Cancer Therapy & Research Center at The University of Texas Health Sciences Center at San Antonio, and Baylor College of Medicine once again hosted the San Antonio Breast Cancer Symposium (SABCS), presenting state-of-the-art breast cancer research to an audience of more than 7,000 clinicians, investigators, and advocates. Jame Abraham, MD, Director of the Breast Oncology Program at the Taussig Cancer Institute of the Cleveland Clinic in Ohio, told The ASCO Post what he considers the biggest news to emerge from the meeting. He comments on each of these studies below.

Be on the lookout for full coverage of these seven “practice-changing” studies in this and future issues of The ASCO Post.

1. Carboplatin as a neoadjuvant therapy for triple-negative breast cancer

Patients with triple-negative breast cancer who received a regimen that included carboplatin had a 60% rate of pathologic complete response, vs 46% for those not receiving this drug—a highly significant increase (odds ratio = 1.76, P = .0018).1

“The role of carboplatin in triple-negative breast cancer has been debated for many years. Finally, we have a randomized study showing that carboplatin will definitely increase the pathologic complete response rate. This study will potentially change how we treat patients with triple-negative disease neoadjuvantly. Of course, we need to wait for long-term data, but at this point, pathologic complete response seems to be a good surrogate endpoint.”

2. Anastrozole for breast cancer prevention in postmenopausal high-risk patients

In the IBIS-II trial, 5 years of anastrozole therapy reduced the risk of primary breast cancer by more than 50% in women at high risk of developing the disease.2

“With the results of IBIS-II, we can clearly say that aromatase inhibitors are as good as, or better than, SERMs [selective estrogen receptor modulators] in preventing breast cancer in postmenopausal women who are at high risk for the disease. Granted, it can be a tough sell. If you look at the penetration of tamoxifen within the population of high-risk patients who are eligible, it’s only about 5% to 10% for prevention at this time. But for the motivated patient at high risk, and after a discussion of the risks and benefits, anastrozole can be a good choice—especially compared to tamoxifen—because some of the major side effects (endometrial cancer and deep-vein thrombosis, for example) are less common. It was also interesting that patients on anastrozole in this trial had a lower incidence of any malignancy, not just breast cancer.”

3. The investigational PARP inhibitor veliparib for triple-negative breast cancer

The I-SPY 2 trial uses an adaptive design to move promising drugs forward in clinical development. In a phase II study evaluating veliparib plus carboplatin for neoadjuvant therapy, the pathologic complete response rate was 52%, vs 26% with chemotherapy alone, in patients with triple-negative breast cancer.3

“The I-SPY trial is important from many different angles. One, the novel innovative trial design shows that we can initiate and conduct studies rapidly, and we can select patients based on their molecular profile and drugs based on their targets. Based on early findings, we can exclude drugs that don’t perform well, or advance the promising drugs in further studies. In this particular study, after disappointing results from other PARP inhibitors (eg, iniparib), we have some promising data, especially for triple-negative breast cancer, and this is exciting. Further phase III studies of veliparib will define its role.”

4. Role of bisphosphonates in postmenopausal women with early breast cancer

The adjuvant use of bisphosphonates reduced the risk of bone recurrence by 34%, and the risk of breast cancer death by 17%.4

“After conflicting reports from large randomized controlled trials, especially AZURE and the ABCSG-12 trial, we have an Oxford Overview analysis that clearly shows the benefit of adjuvant bisphosphonates—especially zoledronic acid—in postmenopausal women. Clearly, this is a practice-changing finding that can be immediately applied in the clinic. The finding that bisphosphonates are highly effective in low-estrogen states is consistent with previously published ABCSG-12 data.”

5. Role of exercise in managing arthralgias induced by aromatase inhibitors

Women randomly assigned to a supervised moderate-intensity exercise program had a 20% reduction in pain scores at 12 months, vs 3% for the usual-care group.5

“The systematic incorporation of exercise as part of the care of patients receiving adjuvant aromatase inhibitors decreased musculoskeletal events and, therefore, should increase compliance with treatment and potentially improve survival. Comprehensive survivorship programs should include an exercise component. It’s extremely important, because we know that 30% of patients discontinue aromatase inhibitors due to side effects.”

6. Role of adjuvant radiation therapy in patients who are older than 65 years

Older women with hormone receptor–positive breast cancer can omit whole-breast radiation therapy after breast-conserving surgery and adjuvant hormone therapy. An exploratory analysis by hormone receptor status showed recurrence rates in estrogen receptor–positive patients to be 3.2% without radiotherapy and 0.8% with radiotherapy, but there was no survival difference.6

“This study shows that radiation can be avoided in patients aged 65 and older. There was no added benefit to radiotherapy, over surgery alone, especially in women with estrogen receptor–positive tumors. There are benefits to avoiding radiation, and these findings are practice-changing.”

7. Affordability and adherence to treatment

A high nonadherence rate (44%) was observed among patients whose copayment exceeded $20 a month.7 Adherence was higher (66%) with generic as compared with branded aromatase inhibitors.

“We could conduct many randomized trials and develop many new drugs, but if our patients cannot afford the medicines, none of these steps will help them. The patient’s copay and other out-of-pocket expenses are key factors in initiating cancer treatment. This study makes a case for greater access to medicine for all patients with cancer. The cost of drugs (and insurance coverage) do matter. Physicians should be sensitive to the ‘financial toxicity’ of their patient’s treatment.”

Disappointments as Well

Most studies presented at the meeting were “winners,” according to Dr. Abraham, but not all. “Unfortunately, there were a few disappointments, and interestingly, two of these studies continued the theme of the failure of anti-VEGF [vascular endothelial growth factor] therapy in breast cancer,” he noted.

Not surprisingly, the phase III BETH trial, which evaluated the addition of bevacizumab (Avastin) to adjuvant chemotherapy and trastuzumab (Herceptin),8 was negative, as was the phase III ROSE/TRIO-12 trial, which evaluated the addition of a new anti-VEGF antibody, ramucirumab, to first-line docetaxel chemotherapy in metastatic breast cancer.9

“We have been hoping that one of these agents would be effective, but so far they have not been,” Dr. Abraham said. “Hopefully, ongoing trials such as the MERiDiAN study will help us find biomarkers that can identify patients who will derive benefit from VEGF-targeted agents.” ■

Disclosure: Dr. Abraham is an unpaid consultant for Pfizer.

References

1. Sikov WM, Berry DA, Perou CM, et al: Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant weekly paclitaxel followed by dose-dense AC on pathologic complete response rates in triple-negative breast cancer: CALGB 40603. 2013 San Antonio Breast Cancer Symposium. Abstract S5-01. Presented December 13, 2013.

2. Cuzick J, Sestak I, Forbes JF, et al: First results of the International Breast cancer Intervention Study II (IBIS-II): A multicentre prevention trial of anastrozole versus placebo in postmenopausal women at increased risk of developing breast cancer. 2013 San Antonio Breast Cancer Symposium. Abstract S3-01. Presented December 12, 2013.

3. Rugo HS, Olopade O, DeMichele A, et al: Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 trial. 2013 San Antonio Breast Cancer Symposium. Abstract S5-02. Presented December 13, 2013.

4. Coleman R, Gnant M, Paterson A, et al: Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomised trials. 2013 San Antonio Breast Cancer Symposium. Abstract S4-07. Presented December 12, 2013.

5. Irwin ML, Cartmel B, Gross C, et al: Randomized trial of exercise vs. usual care on aromatase inhibitor-associated arthralgias in women with breast cancer: The hormones and physical exercise (HOPE) study. 2013 San Antonio Breast Cancer Symposium. Abstract S3-03. Presented December 12, 2013.

6. Kunkler IH, Williams LW, Jack W, et al: The PRIME 2 trial: Wide local excision and adjuvant hormonal therapy ± postoperative whole breast irradiation in women ≥ 65 years with early breast cancer managed by breast conservation. 2013 San Antonio Breast Cancer Symposium. Abstract S2-01. Presented December 11, 2013.

7. Hershman DL, Tsui J, Meyer JW, et al: The change from brand-name to generic aromatase inhibitors and hormone therapy adherence for early stage breast cancer. 2013 San Antonio Breast Cancer Symposium. Abstract S3-04. Presented December 12, 2013.

8. Slamon DJ, Swain SM, Buyse M, et al: Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. 2013 San Antonio Breast Cancer Symposium. Abstract S1-03. Presented December 11, 2013.

9. Mackey JR, Ramos-Vazquez M, Lipatov O, et al: Primary results of ROSE/TRIO-12, a randomized placebo controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. 2013 San Antonio Breast Cancer Symposium. Abstract S5-04. Presented December 13, 2013.



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