Where Does the San Antonio Breast Cancer Symposium Rank

Selected Abstracts From the San Antonio Breast Cancer Symposium

'Best of SABCS' From Jame Abraham, MD, FACP

Jame Abraham, MD, FACP

To each one yr, The ASCO Brand asks Jame Abraham, MD, FACP, Director of the Breast Oncology Platform at Taussig Cancer Institute and Professor of Medicine at the Cleveland Clinic Lerner College of Practice of medicine, to whir his picks for the most important search presented at the 2018 San Antonio Breast Cancer the Crab Symposium. The following are his choices for and comments most studies that may be practice-dynamical. Dr. Ibrahim's comments on these presentations seem in italics.

T-DM1 vs Trastuzumab in KATHERINE Trial

The phase III KATHERINE trial randomly assigned 1,486 patients with residual HER2-positive breast cancer after neoadjuvant therapy to keep on trastuzumab Beaver State be switched to trastuzumab emtansine (T-DM1).¹ T-DM1 reduced the put on the line of an invasive disease–liberated natural selection event at 3 years by 50%. At 3 years, strong-growing disease–free-soil survival was 77.0% with trastuzumab vs 88.3% with T-DM1 (jeopardize ratio [HR] = 0.50; P < .0001). The 11% absolute step-up in invasive disease–free endurance was actually better than the investigators had predicted, and the Kaplan-Meier curves detached early and tended to widen with follow-up.

Clinicians should remember that although T-DM1 is more often than not well tolerated, some patients have side effects.

— Jame Abraham, Doctor, FACP

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All prespecified subgroups benefited from T-DM1, including patients with both operable (HR = 0.47) and unserviceable Cancer (HR = 0.54), internal secretion receptor–negative (HR = 0.50) and endocrine sensory receptor–positive (HR = 0.48) malignant neoplastic disease, node-positivist (HR = 0.52) and client-negative (HR = 0.44) disease, and very flyspeck res disease with unsupportive nodes (60 minutes = 0.60). The striking homogeneity of benefit across all the major subgroups was considered one of the extraordinary findings of the study. The secondary endpoints of disease-free survival and yon recurrence–free interval also showed meaningful reductions in first events with T-DM1. Breast cancer experts agreed that these findings change the standard of care in this patient population, and at that place volition be less tendency to habit pertuzumab advantageous trastuzumab.

Dr. Ibrahim: The results of KATHERINE build on earlier findings for T-DM1. In the EMILIA trial,² T-DM1 improved progress-free survival and overall survival vs lapatinib/capecitabine, and in TH3RESA, these outcomes were improved as compared to trastuzumab plus physician's choice of chemotherapy.³ The results were Thomas More modest in the MARIANNE test,⁴ where T-DM1 did not outperform taxane/trastuzumab combinations, and surprisingly, the addition of pertuzumab to T-DM1 did non growth benefit over T-DM1 alone.

Although MARIANNE diluted the ebullience about T-DM1, the KATHERINE tribulation has brought renewed attention to this drug. Moreover, it has propelled T-DM1 to the front of the line for patients with HER2-positive residual disease after neoadjuvant therapy. Entirely subsets benefited, including patients with whatsoever degree of residual disease. In my view, KATHERINE volition change practice overnight (pending U.S. Food and Drug Governance [FDA] approval), so much as adjuvant trastuzumab did after we heard results of the NSABP B-31 and NCCTG 9831 trials.⁵ T-DM1 wish now be further explored for other patients with immature-stage breast cancer.

Clinicians should remember that although T-DM1 is generally well tolerated, approximately patients have side effects. We must personify blow-by-blow not to neglect the potential for neuropathy, wear, and hepatic toxicity, especially over the long term. Considering the magnitude of the benefit with this drug, I believe many patients leave be willing to pay the price.

Low-Dose Estrogen antagonist for Intraepithelial Neoplasia

A identical low dose of estrogen antagonist—5 Mg/d, given for 3 geezerhood rather than 5 years—halved the risk of breast Cancer recurrence OR new lesions concluded placebo in women with breast intraepithelial neoplasia (ductal carcinoma in situ [DCIS], atypical ductal hyperplasia, lobe carcinoma in situ [LCIS]), without producing the usual toxicities seen with the standard drug, investigators from the phase III Italian TAM01 trial according.⁶ After a median follow-upbound of 5.1 years, 5.5% of patients in the low-dose tamoxifen arm and 11.3% in the placebo limb had disease recurrence or new disease in the front (HR = 0.48; P = .024). Contralateral breast cancer industrial in 12 (4.8%) and 3 (1.2%) patients, respectively (60 minutes = 0.24; P = .018).

To a greater extent FROM SABCS 2018

For more on the studies presented at the San Antonio Breast Cancer Symposium, look for these and other interviews connected The ASCO Post Newsreels at WWW.ascopost.com:

• Andrew D. Seidman, MD, and Charles Stuart E. Geyer, MD, on the KATHERINE trial
• Monica Morrow, Maryland, on lessons learned from upmost abstracts
• Hope S. Rugo, MD, connected immunotherapy for breast cancer
• Reshma Jagsi, MD, DPhil, and Rachel A. Freedman, MD, Miles per hour, on over- and undertreatment of breast cancer
• Kathy S. Albain, MD, on the TAILORx tribulation
• Harold J. Burstein, Atomic number 101, PhD, and Daniel F. Hayes, MD, happening treating lymph node–positive breast cancer

The use of low-dose tamoxifen was associated with an average of only one additional igneous flash per twenty-four hours and no increase in the each day calorific flash score. Reports of vaginal dryness, hurt on intercourse, and musculoskeletal pain or arthralgia were non significantly divers, and treatment adherence was similar to that seen in placebo recipients. Low-dose tamoxifen can be taken as 5 mg/d (cacophonous a 10-mg tablet) or 10 mg every other day.

Dr. Abraham: Although tamoxifen is effective in preventing breast cancer recurrence, its root effects—menopausal symptoms, endometrial cancer, deep-vein thrombosis, and respiratory organ embolism—are barriers to its use as a preclusive step. The aim of this noninferiority study was to determine whether a lower dose and shorter length of tamoxifen would be as hard-hitting as and better tolerated than the standard venereal disease. It was a commonsensible trial to comport, considering that the advisable dose of tamoxifen was at random set, and the optimum dose is actually unknown.

The cumulative incidence of breast events at 5 years was 6.4% with low-Zen estrogen antagonist and 11.0% with placebo, and the relative incidence of serious adverse events was 0.87% and 0.41%, respectively. The benefit found in this study translates into a number needed to treat of 22 and a number needed to harm of 218, which is very favorable.

These findings tell Pine Tree State that I may be healthy to safely reduce the dose for patients World Health Organization do not tolerate tamoxifen, which could help oneself Maine keep patients on discourse. Intelligibly, the side-effect visibility of estrogen antagonist and aromatase inhibitors has inclined the antiestrogens something of a bad report, especially for chemoprevention. It's unclear whether the use of lower doses of estrogen antagonist can change that, but if we can find ways to enhance tolerability so that patients bequeath accept tamoxifen therapy, that will beryllium a very positive development.

Small Differences in Recurrence With Colored-Breast vs Whole-Breast Radiation therapy

Partial-breast irradiation delivered over 5 to 10 days did not meet noninferiority criteria compared with whole-breast irradiation given over 5 to 7 weeks, according to the 10-year results of the large NRG (NSABP B-39/RTOG 0413) trial.⁷ However, the absolute 10-year additive difference in fast-growing boob neoplasm recurrence between the two treated groups was less than 1%, and the absolute cumulative remainder in relapse-slaveless time interval was 1.6%.

The NRG study enrolled 4,216 patients with DCIS surgery stage I or 2 invasive breast cancer with 0 to 3 positive lymph nodes who, subsequently lumpectomy, were willy-nilly assigned to partial-breast irradiation prior to adjuvant chemotherapy (twice day by day treatment with 3.4–3.85 Gy, totaling 10 treatments delivered over 5–10 days using 3-dimensional [3D] conformal external-beam radiotherapy or brachytherapy) or unharmed-breast irradiation after adjuvant chemotherapy (double daily handling with 2 Gy of radiation, to a total of 50 Gy with a sequential boost to the surgical site given over 5–7 weeks). Invasive recurrences were observed in 4.6% of the partial-front irradiation group and 3.9% of the whole-breast irradiation group, for a 0.7% absolute dispute that did not meet the hazard ratio for noninferiority. As supposed, recurrences outside of the primary but still within the bosom were more common with partial-breast irradiation.

Thither may be a misconception, among some physicians and patients, that with cancer treatment, 'much is fitter,' and partial-breast irradiation is therefore underutilized.

— Jame Ibrahim, MD, FACP

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The 10-year cumulative rate of relapse-unoccupied interval was 91.4% with partial-breast irradiation and 93.4% with totally-breast irradiation, an infrangible difference of 1.6% that significantly favored whole-breast irradiation (P = .02). The difference in the 10-year order of distant disease–inexact survival, 96.7% vs 97.1%, respectively, was not statistically significant, nor was the difference in the 10-year overall survival, which was 90.6% and 91.3%, severally. Tier ≥ 3 toxicities were more commons with partial-front irradiation (though not importantly disparate), as were radiation-evoked second cancers. Data on quality of life story and cosmesis were not yet obtainable.

Dr. Abraham: This is the largest test to compare these radiotherapy techniques, and the differences in return-unrestrained musical interval between the two arms, although statistically different, is small, and survival is the same. The authors said that the differences were even smaller in patients receiving partial-white meat light beam via the 3D proficiency (the more modern-day approach), though the study did not compare three methods. I think the findings, therefore, underpin the option of partial-breast irradiation for patients with rude-stage breast genus Cancer who want to undergo breast-conserving surgery, as per the 2016 American Orde for Radiation Oncology (ASTRO) Guidelines.⁸

In that respect may be a misconception, among both physicians and patients, that with cancer treatment, "Sir Thomas More is better," and partial-front irradiation is thence underutilized. For patients, nonetheless, the two approaches vary well in convenience and upper-class of life, as there is a dramatic difference in treatment duration of 5 to 7 weeks vs 5 to 10 years. This meditate suggests partial-knocker ray of light is safe and effectual, and we should be offering it to our patients many often.

Axillary Radiotherapy Is Safe and Effective Aft Positive Sentinel Lymph gland Biopsy

Pursuing identification of a positive sentinel lymph gland, surgical angle lymph node dissection (ALND) and axillary radiation therapy provide excellent and comparable locoregional control and survival, just cavum radiotherapy results in significantly less lymphedema, accordant to 10-year watch over-up of the super AMAROS trial.⁹ In AMAROS, axillary radiotherapy and ALND provided fantabulous and comparable overall natural selection, distant metastasis–free survival, and locoregional control condition.

AMAROS enrolled 4,806 patients with invasive breast tumors measurement 0.5 to 5 mm that were clinically lymph gland-negative. All patients underwent breast-conserving surgery or mastectomy, followed by sentinel node biopsy. The 29.7% of patients with a positive lookout client were further randomized to ALND (n = 744) or axillary radiotherapy therapy (n = 681). The mean figure of sentinel nodes abstracted in both blazonry was two.

Since some women need more treatment and some need fewer, oncologists and surgeons need to tailor therapy according to the case-by-case….

— Jame Abraham, MD, FACP

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At 10 years, return rates were low and similar between the blazon: 0.93% after ALND vs 1.82% after axillary radiotherapy therapy. The range of second primary cancers was higher in the axillary radiation therapy therapy arm (12.09% vs 8.33%; P =. 035). Side personal effects were significantly let down in the axillary radiation therapy sleeve; 5 years afterwards sentinel node biopsy, lymphedema was immediate and/or sunbaked in near 30% of the ALND arm and about 15% in the axillary radiation therapy arm.

Dr. Abraham: Five-year outcomes of the AMAROS study were reportable in 2013, showing no differences in regress between surgery and actinotherapy therapy but to a lesser extent lymphedema with axillary radiation sickness therapy. The study was criticized as being underpowered to show a dispute, due to short reexamination and few events. Now we have the 10-class analysis confirming these findings. We also have several other large trials providing reassurance that we do not have to remove wholly the lymph nodes if the sentinel node is positive and the nodal metastasis is small (not bulky). ACOSOG Z-0011, for one, provided persuasive evidence—same 10-year outcomes—for de-escalating surgery in patients with a positive sentinel lymph node biopsy and clinically perverse nodes.¹⁰

We put up nowadays be sure that de-escalation of therapy reduces the take chances of morbidity for our patients without compromising their outcomes. Since some women need Thomas More treatment and some need less, oncologists and surgeons take to sew therapy according to the individual, simply I hope surgeons will begin to make up more attention to studies such as AMAROS, so that our patients can come through treatment with a better quality of animation.

Circulating Tumor Cell Counts Useful in Whatsoever White meat Cancer Scenarios

In Patients with estrogen receptor–positive, HER2-unfavorable pathologic process breast cancer in whom the benefit of chemotherapy is uncertain, the use of circulating tumor cell (Counterterrorist Center) counts may have some value, accordant to information from a large French randomized trial that evaluated whether CTC counts can help personalize the decision to treat with endocrine therapy or chemotherapy.¹¹ The report concluded that in patients with ≥ 5 CTC/7.5 mL, chemotherapy is preferred over secretor therapy, and that CTC enumerate can be helpful when treatment decisions are discordant.

The 778 patients were randomly assigned to treatment based on a clinical decision vs treatment according to CTC values (< 5 CTC/7.5 mL for tasty of internal secretion therapy and ≥ 5 CTC/7.5 mL for chemotherapy). Patients with low CTC values were viewed atomic number 3 having a good prognosis and were treated with internal secretion therapy only, whereas those with high values received chemotherapy. The sketch met its primary endpoint, showing that progression-free survival was non inferior in the CTC-driven arm, compared with the clinically driven arm.

In 303 patients, there was disagreement American Samoa to the best discourse, and in that discordant mathematical group the utilise of CTCs to guide therapy led to a style for superior outcomes with front-line chemotherapy. Chemotherapy as the selected treatment in this chemical group reduced disease progression risk aside 44% over hormone therapy (HR = 0.66; P = .001), based along a median progression-free survival of 10.5 months with hormone therapy and 15.6 months with chemotherapy. At 2 years, overall survival was also significantly improved (Hour = 0.65; P = .04), from 74.4% to 82.9%. Conversely, when harmony was high between the two decision modes, the two types of treatment yielded similar progression-loose survival and overall survival.

Dr. Abraham: This is the first synchronal discipline reporting a considerable survival benefit by doing CTC examination and the first to show a reduction in the risk of death with front-product line chemotherapy. The results paint a picture that where clinician's choice and CTC-settled recommendations are discordant, there is a slight advantage for chemotherapy. Especially in patients with unfavorable characteristics (such as high CTC count), front-line chemotherapy bum be a suitable pick.

Unitary concern is that the study did non incorporated cyclin-dependent kinase 4/6 inhibitors; therefore, the patients were not treated with a current coming. Also, in the metastatic setting, we are mostly trying to de-escalate therapy, so the approximation of giving chemotherapy instead of endocrine therapy is contrary to it. But the analyse warrants encourage follow-up, and CTC testing deserves additive trials to determine how best to utilize this entropy.

Atezolizumab Compounding in Metastatic Triple-Negative Disease

The phase Troika IMpassion130 visitation, published in 2018 in The New England Journal of Medicine,¹² found that in patients with metastatic triple-dissentient breast cancer the compounding of front-line of merchandise atezolizumab plus nab-paclitaxel significantly built disease-free and general survival. The results were most pronounced in programmed cell death ligand 1 (PD-L1)–positive (≥ 1% expression) disease, and an exploratory analysis reportable in San Antonio confirmed in that location was no benefit from the immunotherapy combination (vs nab-paclitaxel alone) in patients who were PD-L1–negative.¹³

IMpassion130 is the first form III study to demonstrate a survival benefit with immunotherapy in triple-negative breast cancer.

— Jame Abraham, MD, FACP

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In patients with PD-L1–negative disease, the median progression-free survival was identical with atezolizumab/nab-paclitaxel vs placebo/nab-paclitaxel: 5.6 months. By contrast, a 10-month advance in disease-free survival was launch in PD-L1–positive patients aerated with the immunotherapy combination vs placebo plus nab-paclitaxel: 25.5 months vs 15.5 months. There was no significant effect of atezolizumab/arrest-paclitaxel on overall survival in PD-L1–negative patients, whose median overall survival was 18.9 months for immunotherapy vs 18.4 months for chemotherapy. The results of the exploratory analysis of IMpassion130 support the use of atezolizumab plus nab-paclitaxel alone in PD-L1–affirmative triad-counter knocker cancer.

Dr. Abraham: IMpassion130 is the primary phase angle III study to demonstrate a survival benefit with immunotherapy in triple-negative breast cancer. The study showed a clinically meaning progression-non-slave selection and overall natural selection benefit in Pd-L1–positive patients, with a nice breakup of the survival curves, but not in PD-L1–negative patients. These results are somewhat astonishing because studies in other types of cancer have shown a benefit for checkpoint inhibitor therapy in patients with very low levels of Atomic number 46-L1 expression and PD-L1–negative disease.

This explorative analytic thinking of IMpassion130 demonstrated that PD-L1 facial expression in unaffected cells is a highly reliable soothsayer of reception.

— Jame Abraham, Maryland, FACP

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This exploratory analysis of IMpassion130 incontestible that Pd-L1 look in immune cells is a highly reliable prognosticator of reception. They support routine testing for Palladium-L1–positive status in patients with newly diagnosed metastatic and unresectable locally modern triple-negative disease, to determine whether they give the sack benefit from atezolizumab plus nab-paclitaxel. Pending FDA approval, these findings will change the recitation for triple-negative PD-L1 (immune cell)–convinced patients.■

Revelation: Dr. Ibrahim reported no conflicts of interest.

REFERENCES

1. Geyer CE, Huang C-S, Mano MS, et aluminium: Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with res invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE (NSABP B-50-1, GBG 77, and Roche BO27938). 2018 San Antonio Breast Cancer Symposium. Nobble GS1-10. Conferred December 5, 2018.

2. Verma S, Miles D, Gianni L, et alibi: Trastuzumab emtansine for HER2-affirmative late breast cancer. N Engl J Med 367:1783-1791, 2012.

3. Krop IE, Kim Atomic number 51, Martin AG, et al: Trastuzumab emtansine versus treatment of physician's choice in patients with previously doped HER2-positive metastatic breast Crab (TH3RESA): Final overall survival results from a randomised open-label phase 3 trial run. Lancet Oncol 18:743-754, 2017.

4. Perez EA, Barrios C, Eiermann W, et al: Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal outgrowth factor receptor 2-positive, advanced tit Cancer: Important results from the phase III MARIANNE study. J Clin Oncol 35:141-148, 2017.

5. Perez EA, Romond EH, Suman VJ, et aliae: Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patients with HER2-positive breast cancer. 2007 ASCO Annual Confluence. Abstract 512.

6. DeCensi A, Puntoni M, Guerrieri A, et aluminium: A randomised placebo-controlled phase Triad visitation of depleted-dose tamoxifen for the prevention of recurrence in women with operated hormone-sensitive breast ductal or lobe carcinoma in situ. 2018 San Antonio Breast Cancer Symposium. Abstract GS3-01. Presented December 6, 2018.

7. Vicini F, Cecchini R, White J, et al: Chief results of NSABP B-39/RTOG 0413 (NRG Oncology): A irregular stage III learn of conventional whole breast irradiation versus fond tit irradiation for women with stagecoach 0, I, or II breast cancer. 2018 San Antonio Tit Cancer Symposium. Abstract GS4-04. Presented Dec 6, 2018.

8. Correa C, Harris EE, Leonardia MC, et al: Accelerated partial white meat irradiation: Executive summary for the update of an ASTRO evidence-based consensus financial statement. Pract Radiat Oncol 7:73-79, 2017.

9. Rutgers EJT, Donker M, Poncet C, et alii: Radiotherapy or surgical proces of the axilla after a positive sentinel node in breast cancer patients: 10-year follow-up results of the EORTC AMAROS trial. 2018 San Antonio Breast Cancer Symposium. Abstract GS4-01. Conferred December 6, 2018.

10. Giulani A, McCall LM, Beitsch PD, et alia: Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with fast-growing bosom malignant neoplastic disease and spotter node metastasis: The ACOSOG Z0011 (Alliance) irregular nonsubjective trial. JAMA 318:918-926, 2017.

11. Bidard FC, Jacot W, Dureau S, et AL: Clinical utility-grade of circulating tumor cells (CTC) count to take between 1st line hormone therapy & chemotherapy in ER+ HER2– metastatic breast cancer: Results of the phase III clinical trial STIC CTC trial run. 2018 San Antonio Breast Cancer Symposium. Abstractionist GS3-07. Presented December 6, 2018.

12. Schmid P, Sam Adams S, Rugo H, et al: Atezolizumab plus nab-paclitaxel in advanced multiple-negative breast cancer. N Engl J Master of Education 379:2108-2121, 2018.

13. Emens LA, Loi S, Rugo Element 108, et al: Impassion130: Efficacy in immune biomarker subgroups from the global, randomised, double-blind, placebo-controlled phase III clinical trial study of atezolizumab plus nab paclitaxel in patients with treatment-uninitiated, locally advanced Oregon pathological process ternary negative breast cancer. 2018 San Antonio Breast Cancer Symposium. Abstract GS1-04. Presented December 5, 2018.

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Where Does the San Antonio Breast Cancer Symposium Rank

Source: https://ascopost.com/issues/february-10-2019/selected-abstracts-from-the-san-antonio-breast-cancer-symposium/

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