March 2018 VOL 9, NO 3

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Breast Cancer, San Antonio Breast Cancer Syposium

2017 San Antonio Breast Cancer Symposium: Program Highlights

The 40th anniversary of the San Antonio Breast Cancer Symposium was attended by approximately 8000 healthcare professionals and featured presentations ranging from basic science to preliminary clinical trials and new standards of care. Below is a summary of key presentations featured at the press conferences.

Dose-Dense Chemotherapy Improves Outcomes in Early Breast Cancer (Abstract GS1-01)

Increasing the dose density of chemotherapy should become a new standard for the treatment of early breast cancer, according to a large meta-analysis of the Early Breast Cancer Trialists’ Collaborative Group. The meta-analysis included individual patient data from 25 trials with a total of 34,122 women.

The meta-analysis showed that approaches to dose intensification (either shortening the intervals between chemotherapy cycles or giving chemotherapy sequentially) significantly improved the rate of recurrence and breast cancer mortality compared with standard chemotherapy.

A pooled analysis of all 25 dose-intensification trials showed 10-year recurrence rates of 32% with standard chemotherapy versus 28.4% with dose-dense chemotherapy (P = .00001). The 10-year rate of breast cancer mortality was 22.2% with standard chemotherapy versus 19.5% with dose-dense chemotherapy (P = .00001).

Although these seem like modest overall improvements, lead author Richard Gray, MD, said “Chemotherapy reduces mortality by one-third, and dose-dense chemotherapy reduces it by a further 13%, amounting to incremental reductions that nearly cut in half the number of breast cancer deaths.”

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Adjuvant Trastuzumab Not Necessary in HER2-Low High-Risk Breast Cancer (Abstract GS1-02)

The addition of trastuzumab to standard adjuvant chemotherapy did not improve disease-free survival (DFS) in women with early-stage, high-risk invasive breast cancer and low levels of HER2 expression on immunohistochemistry (IHC) or in situ hybridization (ISH), according to results from the NSABP B-47 trial. Patients with “low HER2” represent about 45% of early-stage breast cancer patients and are currently not receiving trastuzumab. Although some studies suggest they might benefit from anti- HER2–targeted therapy, this large study failed to show any benefit.

“It is important to know that current guidelines defining HER2-positive status are valid and ensure that no patients are over- or undertreated. Trastuzumab has serious adverse events, and this study can spare patients from these effects,” said lead author Louis Fehrenbacher, MD, Kaiser Permanente Vallejo Medical Center, Vallejo, CA.

The study enrolled 3270 patients with early-stage breast cancer and low HER2 (IHC1+, IHC2+, and/or ISH negative). Patients were randomized 1:1 to receive standard adjuvant chemotherapy with or without trastuzumab. Five-year invasive DFS was 89.6% in those treated with trastuzumab versus 89.2% among those who did not receive trastuzumab.

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Ribociclib Improves Progression-Free Survival in Premenopausal and Postmenopausal Women with Hormone Receptor–Positive Advanced Breast Cancer (Abstract GS2-05)

The addition of the CDK4/6 inhibitor ribociclib to standard frontline endocrine therapy with temporary ovarian suppression significantly improved progression-free survival (PFS) in premenopausal and perimenopausal women with advanced hormone receptor (HR)-positive, HER2-negative breast cancer in the phase 3 MONALEESA-7 trial.

Although CDK4/6 inhibitors are FDA approved in combination with hormonal therapy (either aromatase inhibitor [AI] or fulvestrant) for postmenopausal women with advanced HR-positive, HER2-negative disease, this is the first randomized trial to show that this is a good treatment option for younger premenopausal or perimenopausal women (approximately 40% of all HR-positive, HER2-negative advanced breast cancers).

“It is also the first trial to show that ribociclib can be safely and effectively combined with either tamoxifen or a nonsteroidal AI together with ovarian suppression using goserelin,” said lead author Debu Tripathy, MD, The University of Texas MD Anderson Cancer Center in Houston.

“This is a potential new treatment for premenopausal women with HR+, HER2-negative, advanced breast cancer, regardless of disease-free interval or endocrine partner,” Dr Tripathy said.

The study enrolled 672 patients: 335 were randomized to ribociclib plus either tamoxifen or AI and goserelin, and 337 were randomized to the same hormonal therapy and goserelin with placebo. The study met its primary end point. Median PFS was significantly better in the ribociclib arm: 23.8 months compared with 13 months in the placebo arm, representing a 45% improvement favoring ribociclib (P = .0000000983).

The benefit of the addition of ribociclib was consistent across all patient subgroups, regardless of endocrine partner. Safety was manageable and predictable. Patients who received ribociclib had a clinically meaningful improvement in time to deterioration of quality of life and improvement in pain score compared with patients in the placebo arm.

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Combination of Pembrolizumab plus Trastuzumab Encouraging in Trastuzumab-Resistant HER2-Positive Breast Cancer (Abstract GS2-06)

The combination of pembrolizumab plus trastuzumab was well tolerated and provided clinical benefit in patients with trastuzumab-resistant, HER2-positive, advanced breast cancer in the phase 1b/2 PANACEA trial.

The combination of pembrolizumab/trastuzumab met its primary end point with an objective response rate (ORR) of 15% and a disease control rate (DCR) of 25% at 6 months or more among 58 patients with HER2-positive, advanced breast cancer that had become resistant to trastuzumab. Median follow-up was 13.6 months.

It appears that patients who are PD-L1–positive and have ≥5% circulating tumor-infiltrating lymphocytes (TILs) have the best response to the immunotherapy combination. In a subgroup of 40 patients with PD-L1–positive disease and ≥5% TILs in the metastatic lesion, ORR was 39%, and DCR was 47%. This suggests that quantifying TILs can help select patients who will derive the most benefit from this combination. No responses were observed in the 18 patients who were PD-L1–negative.

“This proof-of-principle study suggests that immune evasion is a mechanism of resistance to trastuzumab and contributes to disease progression in advanced HER2-positive breast cancer,” said lead author Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, on behalf of the International Breast Cancer Study Group.

“These are the best data we have on immunotherapy in HER2-positive breast cancer. If future studies pan out, we will have more options to treat this disease. This study gives us a good signal to continue to study immunotherapy in HER2-positive disease in combination with anti-HER2 therapy,” commented press conference moderator, Virginia Kaklamani, MD, The University of Texas Health Science Center, San Antonio.

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Two Years of Extended AI Therapy Better Than 5 Additional Years (Abstract GS3-01)

Two years of additional aromatase inhibitor (AI) therapy after 5 years of endocrine therapy was just as effective as 5 additional years for treatment of postmenopausal women with hormone receptor (RH)-positive breast cancer, according to results of the large ABCSG-16 trial.

Extending AI for 2 years or for 5 years achieved similar rates of disease-free survival, overall survival, time to contralateral breast cancer, and time to second primary cancer. The rate of clinical fracture was slightly higher in the 5-year arm: 6% versus 4.7%.

“We can now conclude that after 5 years of adjuvant endocrine therapy, 2 more years of AI is sufficient. There is no benefit from 5 additional years of AI, and 5 more years lead to more clinical fractures and should be avoided,” said lead author Michael Gnant, MD, Medical University of Vienna, Vienna, Austria. “The take-home message is that we can avoid unnecessary treatment and side effects by giving only 2 years of additional AI instead of 5 years.”

“There was no benefit in the highest risk subgroups or for those who were adherent. For the vast majority of patients with luminal breast cancer, the most common type of breast cancer, a total of 7 years of additional AI is sufficient,” Dr Gnant said.

The study included 3484 women with HR-positive breast cancer who received 5 years of endocrine therapy (either tamoxifen, AI, or tamoxifen followed by AI) and were then randomized to receive 2 more years of anastrozole versus 5 more years of anastrozole. Patients were recruited from 75 centers in Austria, and median follow-up was 106.2 months.

“For many years we have treated too many people for too long. De-escalation of therapy is a trend for HER2-positive and estrogen receptor–positive breast cancer. This is all good news. We don’t need another randomized trial to prove we are not depriving patients with only 7 years of adjuvant endocrine therapy,” said press conference moderator Carlos Arteaga, MD, Director of the Harold C. Simmons Comprehensive Cancer Center at The University of Texas Southwestern Medical Center, Dallas, TX.

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Nab-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer (GS3-05)

Substituting nab-paclitaxel for paclitaxel as part of neoadjuvant chemotherapy improved disease-free survival (DFS) in patients with high-risk early breast cancer over the long term, according to results of the phase 3 GeparSepto study.

The large study, conducted at 69 centers, randomized 1200 patients with nonmetastatic early breast cancer to either 12 weekly cycles of paclitaxel or 12 weekly cycles of nab-paclitaxel, each followed by 4 cycles of epirubicin/cyclophosphamide. All patients with HER2-positive disease also received trastuzumab and pertuzumab.

Patient and tumor characteristics were well balanced between the treatment arms.

The 3-year DFS rate was 87.1% with nab-paclit­axel versus 80.7% with standard paclitaxel (hazard ratio, 0.69; 95% CI, 0.54-0.89; P = .0044). The absolute difference between treatment groups was 6.4%. At 4 years, DFS was 83.5% versus 76.2%, respectively, for an absolute improvement of 7.3%.

Subgroup analysis showed that nab-paclitaxel improved DFS in all subgroups, including biological subtype, HER2 status, estrogen receptor/progesterone receptor status, and low versus high Ki67.

Overall survival data are not yet mature.

“These long-term data are important, because so far 61% of the DFS events that have occurred in Gepar-Septo are distant relapses,” said Andreas Schneeweiss, MD, University of Heidelberg, Germany, who presented the data.

At another session, Eric Winer, MD, of the Dana-Farber Cancer Institute, Boston, MA, said that he needs more data before substituting nab-paclitaxel for paclitaxel as part of adjuvant or neoadjuvant therapy in routine clinical practice. “I would not use this outside of a clinical trial,” he stated. He noted that the labeling dose is too high and that lower doses can reduce toxicity.

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