Charles L Shapiro, MD, FASCO

Insights from the 2018 San Antonio Breast Cancer Symposium

Question

Please summarize what you feel were the 5 most important presentations from the 2018 San Antonio Breast Cancer Symposium (SABCS 2018)? (List 5 abstract titles or trial names)

Answer

From my perspective there were 6 very important presentations in San Antonio, which were presented during general sessions throughout the conference.

• Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: primary results from KATHERINE.¹
• IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer.²
• Alpelisib + fulvestrant for advanced breast cancer: Subgroup analyses from the Phase III SOLAR-1 trial.³
• A randomized placebo controlled phase III trial of low dose tamoxifen for the prevention of recurrence in women with operated hormone sensitive breast ductal or lobular carcinoma in situ.⁴
• RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT).⁵
• Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer.⁶

Question

Why are these findings important and what are the clinical implications for these data?

Answer

The KATHERINE trial is a practice changing trial in which trastuzumab emtansine (TDM-1) was shown to be superior to trastuzumab in patients who had residual disease after neoadjuvant HER2-targeted chemotherapy. This data revealed that TDM-1 is a new standard for these patients.¹

The Impassion130 trial was a randomized placebo-controlled trial of nab-paclitaxel with or without atezolizumab in patients with metastatic triple-negative breast cancer. Overexpression of the PDL1 receptor in the tumor predicted for benefit. Based on these findings, I would say that patients with triple-negative breast cancer with PDL1 overexpression have the option of a new standard of care. However, it must be noted that atezolizumab has unique rare toxicities like pneumonitis, endocrinopathies, myocarditis, and colitis that can be life-threatening if they are not recognized and appropriately treated.²

The SOLAR-1 trial presentations highlighted the outcomes of a randomized, placebo controlled trial of alpelisib with or without fulvestrant for the second-line treatment of estrogen receptor-positive metastatic breast cancer with PI3-kinase mutations in the tumor. Final outcomes of the trial indicated that the combination therapy was superior to fulvestrant alone. This drug is a specific inhibitor of alpha-subunit of the PI3-kinase protein, which is in contrast to previous PI3-kinase inhibitors that targeted the whole protein. The results of this study will stimulate subsequent trials that look into the use of alpelisib and other drugs (CDK4,6 inhibitors) that improve outcomes for the most frequent population of estrogen receptor-positive metastatic disease.³

TAM-01 findings outlined a placebo-control trial that revealed tamoxifen at 5 mg was effective preventing breast cancer in high-risk women. Given that the current standard dose for these patients is 20 mg, these findings were in line with an overall meeting theme of treatment de-escalation.⁴

The 5 mg dose was not associated with endometrial cancer and blood clots, very rare side effects of the 20 mg dose. The RAPID trial and NSABP B-39/RTOG 0413 were both randomized trials that compared whole breast radiotherapy with partial breast radiation, which shortens the course of radiation. Both trials showed that the clinical outcomes (disease-free and overall survival) were about the same between patients who received partial breast radiation and standard whole breast radiation. However, it is important to note that the cosmetic result of breast radiation was found to be worse over time in partial breast radiation in one study,⁵ and was not reported in another study.⁶

Question

A current theme in the treatment of patients with breast cancer is treatment de-escalation. What were the main takeaways from SABCS 2018 regarding treatment duration and optimal sequencing strategies?

Answer

We have identified the importance of de-escalated treatments sentinel biopsy, radiation therapy is equivalent to axillary dissection, and sparing adjuvant chemotherapy for many women. We know that we are overtreating many women with breast. Ongoing efforts to identify patients that will benefit from treatment de-escalation as well as identifying the women who really need and will benefit most from treatments.

Question

Based on the research presented at SABCS 2018, what are you looking forward to in terms of future developments in the treatment of patients with breast cancer?

Answer

There were many presentations that involved genomics. We are beginning to deepen our understanding what makes cancer different from normal tissues and this will inevitably lead to better treatments that prolong survival in patients with breast cancer as well prevent breast cancer. We also are identifying the women who don’t need treatment or who would benefit from less treatment. The near term future is very hopeful for women with breast cancer.

References

1. Geyer, Jr. CE, Huang C-S, Mano MS, et al. Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS1-10.

2. Emens LA, Loi S, Rugo HS, et al. IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS1-04.

3. Juric D, Ciruelos E, Rubovszky G, et al. Alpelisib + fulvestrant for advanced breast cancer: Subgroup analyses from the phase III SOLAR-1 trial. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS3-08.

4. DeCensi A, Puntoni M, Guerrieri Gonzaga A, et al. A randomized placebo controlled phase III trial of low dose tamoxifen for the prevention of recurrence in women with operated hormone sensitive breast ductal or lobular carcinoma in situ. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS3-01.

5. Whelan T, Julian J, Levine M, et al. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT). Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS4-03.

6. Vicini FA, Cecchini RS, White JR, et al. Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS4-04.