Recent advancements in the field of breast cancer are reshaping the treatment paradigm for subsets of patients with the disease, bringing new therapies and strategies into focus, according to experts who participated in an 

The panelists said research from key abstracts presented during the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5-9 in Texas, generated fresh insights into the treatment of pre- and perimenopausal women with hormone receptor (HR)-positive disease, emerging antibody—drug conjugates for HER2-positive and triple-negative breast cancer (TNBC), and the potential for immunotherapy. The experts were particularly enthusiastic about the continuing exploration of CDK4/6 inhibitors, a class of drugs that has emerged since 2015 for women with HR-positive, HER2-negative breast cancer. They also noted the expansion of PARP inhibitors from ovarian to breast cancer. In January 2018, the FDA approved olaparib (Lynparza), a PARP inhibitor, for patients with metastatic HER2-negative disease and a germline 

 mutation after prior treatment with chemotherapy.

“I think the science in breast cancer is really making tangible differences in our patients’ lives now and that’s exciting,” said Lee S. Schwartzberg, MD.

Three CDK4/6 inhibitors are now approved for patients with metastatic, HR-positive, HER2- negative breast cancer. Palbociclib (Ibrance) was the first agent approved in this drug class in 2015, followed by abemaciclib (Verzenio) and ribociclib (Kisqali) in 2017. These therapies have been targeted for postmenopausal women.

Research at SABCS is likely to expand that population. “We now have another option that is formally clinically tested for premenopausal women—to use ovarian suppression and an aromatase inhibitor [AI],” said Schwartzberg.

According to the phase III MONALEESA-7 trial, adding ribociclib to first-line endocrine therapy (tamoxifen/nonsteroidal AI with goserelin) significantly prolongs progression-free survival (PFS) in both pre- and perimenopausal women with HR-positive, HER2-negative advanced breast cancer.1

That’s significant because “a lot of times, people think you have to take the ovaries out of these patients,” said Hope S. Rugo, MD. “Now we know we don’t have to take the ovaries out.”

Adding ovarian suppression to tamoxifen therapy improves outcomes in premenopausal women with HR-positive, HER2-negative breast cancer; the combination of an AI plus ovarian suppression may be even more beneficial, according to updated data from the TEXT and SOFT trials. “One thing that was really striking to me was that women who were under the age of 35 had this enormous benefit,” Rugo said. “There was more than a 15% difference in disease-free survival (DFS) in patients who got aromatase inhibitor plus ovarian suppression versus tamoxifen, and then an 11.5% benefit in patients who got tamoxifen plus ovarian suppression. What that means is you can give patients either option.”

However, toxicities seem to be more common in patients treated with AIs, and that’s an important factor to consider. “We’re already making women miserable enough with luteinizing hormone— releasing hormone suppression. We make them more miserable with an AI on top of it,” said session moderator Adam M. Brufsky, MD, PhD.

CDK4/6 inhibition plus an AI has also been shown to improve PFS and quality of life in postmenopausal women with HR-positive, HER2-negative advanced breast cancer.2 That’s “very important in the metastatic and palliative setting,” said Komal Jhaveri, MD, noting that available data also suggest significant reductions in pain scores by 8 weeks. The fact that CDK4/6 inhibition doesn’t seem to disrupt quality of life means it may also be a good option for asymptomatic patients with metastases.

“If you give chemo, their quality of life is worse, even though the scans look better,” Francisco J. Esteva, MD, PhD, said. “The fact that quality of life was improved with ribociclib and letrozole was very reassuring.”

“Neoadjuvant therapy for HER2-positive breast cancer has been a tremendous success. What we’re trying to do now is refine it,” Brufsky said. What, for instance, is the optimal chemotherapy backbone for use with trastuzumab (Herceptin)/ pertuzumab (Perjeta)? A retrospective stage II to III study of 226 patients

 determined that “the pathologic complete response [pCR] rate was higher in patients treated with THP (taxane/trastuzumab/ pertuzumab), which is interesting because you would think TCHP [taxane/carboplatin/trastuzumab/ pertuzumab] or THP followed by AC [cyclophosphamide/carboplatin] would give you a higher pCR,” Esteva said. “It’s something to keep in mind: Some patients may do very well with THP.”

Also in question: the optimal length of treatment. The SOLD study, a phase III trial, compared 9 weeks of adjuvant trastuzumab versus the standard 12 months, in combination with adjuvant taxaneanthracycline chemotherapy in 2176 patients with early HER2-positive breast cancer. Rugo questioned the choice of a 9-week regimen—“Nine weeks is a funny choice. Couldn’t you give them 12?”&mdash;but she applauded the intent behind the research.

“This is a really important question for a number of reasons. One is that the original trials never really asked how long the optimal duration of trastuzumab treatment was. The second is that most people in the world can’t afford trastuzumab,” Rugo said.

The 9-week treatment regimen did not meet the noninferiority criteria. However, the subset of patients who received 100 mg/m2 “seemed to do just as well with 9 weeks versus 12 months,” Rugo said. However, she doesn’t plan on decreasing the duration of treatment for most patients. “Our gold standard is still 12 months,” she said.

Adding trastuzumab to standard adjuvant chemotherapy for tumors expressing low levels of HER2 protein is not advised. The NSABP B-47 phase III trial found that adding trastuzumab did not significantly affect invasive DFS.

 “I was actually happy about that result,” Schwartzberg said. “It would have rocked my world if we thought we knew the target and had a test to identify the target and then we didn’t.”

Novel approaches for metastatic HER2- positive disease include trastuzumab deruxtecan (DS-8201), an antibody—drug conjugate that Brufsky nicknamed “TrasD.”

“This one is a topoisomerase 1 inhibitor,” Jhaveri said. A phase I trial presented at the symposium included 2 cohorts: a HER2-positive cohort that was pretreated with either ado-trastuzumab emtansine (T-DM1; Kadcyla) or T-DM1/pertuzumab, and a HER2—low expression cohort.

 “In both of these, there was activity seen,” Jhaveri said. Additionally, “there was not increased toxicity, and duration of response was really, really impressive, in some patients as long as 1-and-ahalf years into the study,” she said.

Nab-paclitaxel (Abraxane) may lead to increased PFS in women with locally recurrent or metastatic breast cancer.

According to Rugo, who participated in the CALGB 40502/NCCTG N063H trial for patients with TNBC, “when we looked at the subset analysis of estrogen receptor—positive and triple-negative disease, we saw this superiority in the triple-negative group, which is fascinating.”

The phase III GeparSepto trial, which randomized patients to paclitaxel versus nab-paclitaxel followed by AC in both groups, also showed a “much higher” pCR rate in the triple-negative population, Esteva said. “Interestingly, [regardless of] pCR, the event-free survival was significantly better for patients treated with nab-paclitaxel compared with paclitaxel,” he said. So, should clinicians use nab-paclitaxel instead of paclitaxel in triple-negative patients? That’s a “hard call,” Rugo said. “I think that these data as yet aren’t enough to say you should already be using nab-paclitaxel.”

Jhaveri agreed. “Outside of a clinical trial, I’m not sure I am going to personally change my practice. I think we need some kind of validation, at least in the early-stage setting, to be able to justify a 75% grade 1/2 peripheral neuropathy from nab-paclitaxel,” she said.

For women with germline BRCA mutations, there’s a new standard of care: PARP inhibitors—olaparib and talazoparib (BMN-673). The phase III EMBRACA study compared talazoparib, an oral PARP inhibitor, to physician’s choice of therapy; PARP therapy significantly prolonged PFS and was well tolerated.

 That finding led Schwartzberg to suggest “germline testing on all metastatic patients.”

“Every triple-negative patient should be tested. The prevalence is high enough, and now you have a new agent,” he said.

Immunotherapy also may be an emerging treatment for triple-negative breast cancer. In the KEYNOTE-086 trial, the objective response rate (ORR) to pembrolizumab monotherapy was 23% in patients with PD-L1—positive, previously untreated metastatic cancer; 3 of the 84 enrolled patients experienced a complete response.

“We’re looking at an explosion of studies now and a lot of excitement,” Rugo said. “Hopefully, we’ll be able to hone it down and figure out who’s going to respond and how we can best capitalize on that.”

Sacituzumab govitecan (IMMU-132), an antibody—drug conjugate, is another promising therapy for TNBC. According to a phase II study presented at the symposium, treatment with sacituzumab elicited an ORR of 34% in patients with heavily pretreated metastatic TNBC.

“The target sacituzumab is looking at is a protein called TROP-2, which is a surface glycoprotein that is expressed in more than 90% of triple-negative breast cancers,” Jhaveri said, noting that the drug received FDA breakthrough therapy designation for the treatment of patients who have failed at least 2 prior therapies for metastatic disease.

This was an exciting year for various reasons,” Jhaveri said. “We have our first PARP inhibitor for our 

-mutant patients. We have exciting new drugs, including the antibody—drug conjugates, and it was nice to see data specifically focused on subgroups include premenopausal patients, where we now have CDK4/6 inhibitor data. It was nice to see a confirmation of our biases in certain areas, including ovarian function suppression, and to have new drugs to offer our patients.”

Tripathy D, Sohn J, Im SA, et al. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2- negative advanced breast cancer: results from the randomized phase III MONALEESA-7 trial. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS2-05. www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828&terms=.

Singh H, Howie LJ, Bloomquist E, et al. A U.S. Food and Drug Administration pooled analysis of outcomes of older women with hormone-receptor positive metastatic breast cancer treated with a CDK4/6 inhibitor as initial endocrine based therapy. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS5-06. abstracts2view.com/sabcs/view. php?nu=SABCS17L_1028&terms=.

Rashmi MK, Akshara RS, Kenneth HR, et al. Patterns of use and effectiveness of neoadjuvant pertuzumab-containing regimens in stage II-III HER2-neu positive breast cancer: A retrospective, single institutional experience. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract P5-20-10. abstracts2view.com/sabcs/view.php?nu=SABCS17L_1398&terms=.

Fehrenbacher L, Cecchini RS, Geyer CE, et al. NSABP B-47 (NRG oncology): Phase III randomized trial comparing adjuvant chemotherapy with adriamycin (A) and cyclophosphamide (C) à weekly paclitaxel (WP), or docetaxel (T) and C with or without a year of trastuzumab (H) in women with node-positive or high-risk nodenegative invasive breast cancer (IBC) expressing HER2 staining intensity of IHD 1+ or 2+ with negative FISH (HER2-Low IBC). Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS1-02. abstracts2view.com/sabcs/view. php?nu=SABCS17L_989&terms=.

Modi S, Tsurutani J, Takahashi S, et al. Safety and efficacy results from a phase 1 study of DS-8201a in patients with HER2 expressing breast cancers. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract PD3-07. abstracts2view. com/sabcs/view.php?nu=SABCS17L_1094&terms=.

Rugo HS, Barry WT, Moreno-Aspitia A, et al. Long-term follow-up of CALGB 40502/NCCTG N063H (Alliance): a randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) +/- bevacizumab as firstline therapy for locally recurrent or metastatic breast cancer (MBC). Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS3-06. abstracts2view.com/sabcs/ view.php?nu=SABCS17L_1333&terms=.

Litton J, Rugo HS, Ettl J, et al. EMBRACA: A phase III trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA mutation. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS6-07. abstracts2view.com/sabcs/ view.php?nu=SABCS17L_1735&terms=.

Adams S, Loi S, Toppmeyer DL, et al. KEYNOTE-086 cohort B: pembrolizumab monotherapy for PD-L1-positive, previously untreated, metastatic triple-negative breast cancer (mTNBC). Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract PD6-10. abstracts2view.com/sabcs/view. php?nu=SABCS17L_1074&terms=.

Bardia A, Vahdat LT, Diamond J, et al. Sacituzumab govitecan (IMMU132), an anti-Trop-2-SN-38 antibody-drug conjugate, as ≥3rd-line therapeutic option for patients with relapsed/refractory metastatic triple-negative breast cancer (mTNBC): efficacy results. Presented at: 2017 San Antonio Breast Cancer Symposium; San Antonio, Texas, December 5-9, 2017. Presentation GS1-07. abstracts2view.com/sabcs/ view.php?nu=SABCS17L_1727&terms=.

Articles

Recent advancements in the field of breast cancer are reshaping the treatment paradigm for subsets of patients with the disease, bringing new therapies and strategies into focus.

HR-Positive Advances Highlight the Good News in Breast Cancer

Although chemotherapy remains the mainstay of treatment for patients with triple-negative breast cancer (TNBC), promising developments are unfolding on several fronts, including new ways of using existing therapies and the exploration of immunotherapy, novel antibodies, and agents targeting the PI3K/mTOR/AKT pathway. A paucity of biomarkers to predict for responders remains one of the most significant challenges impeding progress, according to David W. Miles, MB BS, BSc, MD, FRCP.

In a presentation during the 1st Annual Paris Breast Cancer Conference hosted by the Physicians Education Resource

, LLC, Miles, a consultant medical oncologist at West Hertfordshire Hospitals in England, provided his perspective on potential new treatment options for patients with TNBC.

In everyday practice, treatment for patients with TNBC typically includes chemotherapy. “[For] those of us working out in the peripheral hospitals and seeing lots of patients, we are still stuck with chemotherapy,” said Miles. “We say to our patients, ‘I’m sorry the endocrine treatment isn’t going to work, I’m sorry HER2 isn’t a target, so we’re really going to hit as hard as we can with chemotherapy,’ even for those in relatively low-risk situations in the adjuvant setting.”

In the phase II tnAcity study, 3 combinations of these drugs were tested in the frontline setting for patients with metastatic TNBC. The combination of nab-paclitaxel and carboplatin showed the highest progression-free survival (PFS) rate at 7.4 months, compared with 5.4 months with nab-paclitaxel and gemcitabine and gemcitabine plus carboplatin at 6.0 months (Table).

 Overall survival (OS) was also increased with the nab-paclitaxel/carboplatin combination.

Table. Survival Rates of Combinations in the tnAcity Trial

Miles noted that the trial was not progressing to phase III due to the evolving treatment landscape, but he suggested considering a platinum-containing regimen for these patients.

Miles also argued that there was a role for bevacizumab (Avastin) in TNBC, especially for patients who have received a taxane, based on prior subgroup analyses. In the phase III MERiDiAN trial, patients with HER2-negative metastatic breast cancer, including those with TNBC, received paclitaxel with or without added bevacizumab. In the overall population, the median PFS was 11.0 months with the combination versus 8.8 months with paclitaxel and placebo (hazard ratio [HR], 0.68; 95% CI, 0.51-0.91; P = .0007).2

In searching for a biomarker for response for this regimen, Miles et al tested patients for their plasma VEGF-A levels in the study. Yet the results indicated that baseline plasma VEGF-A levels are not predictive of a clinically relevant difference in treatment effect with the addition of bevacizumab. “Angiogenesis is a very complex behavior, [so] it may be naïve to think that 1 biomarker is going to do it for us,” Miles said.

“I would have to describe immunotherapy as the dominant strategy at the moment,” commented Miles, as several PD-1/PD-L1 checkpoint inhibitors are currently being tested for patients with TNBC.

In a study of atezolizumab (Tecentriq) in the frontline or in later lines of therapy, patients with TNBC showed an objective response rate (ORR) of 26% (95% CI, 9%-51%) with the PD-L1 inhibitor in the frontline; in the second line and beyond, the ORR was 7%.3 He also noted that with traditional measurements in clinical trials, such as PFS, immunotherapy agents may not demonstrate significant benefit. In this trial of atezolizumab, for example, the median PFS was 1.4 months by RECIST v1.1 criteria and 1.9 months by immune-related response criteria. The benefit seen, however, was much greater when looking at duration of response, which was 21.1 months by both sets of criteria.

Additionally, the study also showed a higher ORR among patients with positive PD-L1 expression compared those with negative expression, yet Miles noted that he found PD-L1 expression to be a transient biomarker of utility. Other biomarkers— tumor-infiltrating lymphocytes, CD8-positive T cells, and PD-L1 expression on immune cells&mdash;may be associated with better outcomes, but they are not yet predictive. Instead, he stressed, they may simply identify patients with a better prognosis.

Combination trials of chemotherapy with immunotherapy are inevitable, according to Miles, and have shown some encouraging findings, yet these are still only in small numbers of patients. A phase Ib/II study of pembrolizumab (Keytruda), a PD-1 inhibitor, combined with eribulin (Halaven) demonstrated promising responses in 39 evaluable patients with metastatic TNBC in the frontline setting and beyond. The ORR was 41.2% in the frontline and 27.3% in the second line and beyond, demonstrating a clear benefit earlier in the course of disease.4 Miles noted that the use of eribulin here was important because many of these patients would have received a platinum-containing regimen in the first line.

“When you’ve got chemotherapy in the backbone, PD-L1 expression doesn’t differentiate those patients who respond versus those who don’t,” he noted, as the ORR in PD-L1—positive patients was 29.4% compared with 33.3% in PD-L1–negative patients.

The results of several ongoing trials of immunotherapy agents may help shape the course of future trials for patients with TNBC, according to Miles. The ongoing trials include 2 studies of pembrolizumab: 1 phase III trial compares pembrolizumab with single-agent chemotherapy in previously treated patients (KEYNOTE-119; NCT02555657), and 1 compares pembrolizumab with nab-paclitaxel or paclitaxel or gemcitabine/carboplatin in the frontline (KEYNOTE-355; NCT02819518).

There are also 2 ongoing studies of atezolizumab: 1 is studying nab-paclitaxel with or without added atezolizumab in the frontline (IMpassion 130; NCT02425891), and 1 is examining paclitaxel plus or minus atezolizumab (IMpassion 131; NCT03125902) for patients with no prior therapy for metastatic or locally advanced disease.

The subset of TNBC patients who express the androgen receptor (AR) generally demonstrate a longer disease-free interval in early-stage disease, Miles said. In a single-arm, 2-stage, phase II trial of hormonal therapy with enzalutamide (Xtandi), the median PFS was 12.6 weeks (95% CI, 8.1-15.7).5 For patients with AR expression ≥10%, the median PFS was 14.7 weeks, and in patients with low AR expression <10%, the median PFS was 8.1 weeks. “You can see some possible correlation between the degree of androgen receptor expression and the resultant progression-free survival,” he said.

In the patients who expressed the PREDICT AR genomic signature of an AR-driven biology, about 50% of patients in this study, the median PFS was 3.7 months, compared with 1.8 months in patients who did not express this signature. “These are what people would call hypothesis-generating for the purpose of the next study,” said Miles. The next step with this agent was supposed to be the phase III ENDEAR study of enzalutamide with or without paclitaxel in advanced TNBC, but this study was discontinued.

Glembatumumab vedotin, a glycoprotein NMB (gpNMB)-targeting antibody—drug conjugate, was investigated in the small phase II EMERGE study compared with investigator’s choice of chemotherapy, and it showed a small ORR of 6% versus 7% with chemotherapy.6 However, in patients expressing gpNMB in ≥25% of their tumor cells, the ORR was 30% with glembatumumab vedotin and 9% with chemotherapy. In patients with the gpNMB marker, not just gpNMB expression, the ORR was 40% with glembatumumab vedotin versus 0% with chemotherapy in a posthoc analysis. “This to me seems very promising,” Miles said. “It seems like a validatable and an identifiable target that could be done in a relatively straightforward way, in a less complex fashion than immunology or angiogenesis.”

Findings from the EMERGE study led to the opening of the METRIC trial, which will randomize patients 2:1 to glembatumumab vedotin or capecitabine and use PFS as the primary endpoint (NCT01997333). Miles said that METRIC’s results are highly anticipated.

Sacituzumab govitecan (IMMU-132), a humanized immunoglobulin G antibody against Trop-2, received a breakthrough therapy designation for the treatment of previously treated patients with metastatic TNBC in February 2016. The phase II study showed that the ORR was 30%, the median PFS was 6.0 months (95% CI, 5.0-7.3), and the median OS was 16.6 months (95% CI, 11.1-20.6) with sacituzumab govitecan.7 Miles said this looked like a promising approach.

Of particular interest to Miles was the use of MEK inhibition with cobimetinib (Cotellic), as MEK may confer resistance to taxanes. Cobimetinib combinations are being investigated in the multiple-cohort COLET trial. Findings presented at the 2017 San Antonio Breast Cancer Symposium demonstrated an ORR of 38.3% among patients (n = 47) with previously untreated locally advanced or metastatic TNBC who received cobimetinib plus paclitaxel comparedwith a 20.9% ORR among those who received paclitaxel plus placebo (n = 43).8 Trial is continuing with cohorts testing the cobimetinib plus atezolizumab with paclitaxel or nab-paclitaxel (NCT02322814).

In the LOTUS trial, patients with metastatic TNBC were treated with the AKT inhibitor ipatasertib. The study looked at PFS overall and in patients with low PTEN expression, but the study also examined OS in patients with PI3K/AKT pathway-activated tumors as a secondary endpoint.9 Miles noted that, consistent with literature, a majority of patients with PTEN-low tumors by immunohistochemistry testing do not have a genetic alteration.

In the overall population (n = 124), the stratified HR for PFS was 0.60 (90% CI, 0.40-0.91), favoring the combination with ipatasertib; in the PTENlow subgroup (n = 48), the HR was 0.59 (90% CI, 0.30-1.16); and for patients with PIK3CA/AKT1/ PTEN-altered tumors, the unstratified HR was 0.44 (90% CI, 0.20-0.87). While Miles commented that a valiant attempt has been made to explore these targets of the PI3K/mTOR/AKT pathway, “[we may] need to look at a more molecular level at that pathway and at what drives it,” he said.

Yardley D, Coleman R, Conte P, et al. Nab-paclitaxel + carboplatin or gemcitabine vs gemcitabine/carboplatin as first-line treatment for patients with triple-negative metastatic breast cancer: results from the randomized phase 2 portion of the tnAcity trial. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P5-15-03. sabcs.org/ Portals/SABCS2016/Documents/SABCS-2016-Abstracts.pdf?v=1.

Miles DW, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): a double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. 

2017;70:146-156. doi: 10.1016/j.ejca.2016.09.024.

Schmid P, Cruz C, Braiteh FS, et al. Atezolizumab in metastatic TNBC (mTNBC): long-term clinical outcomes and biomarker analyses. Presented at: 2017 American Association for Cancer Research Annual Meeting; April 1-5, 2017; Washington, DC. Abstract 2986. abstractsonline.com/pp8/#!/4292/presentation/1296.

Tolaney S, Savulsky C, Aktan G, et al. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P5-15-02. sabcs.org/Portals/ SABCS2016/Documents/SABCS-2016-Abstracts.pdf?v=1.

Traina TA, Miller K, Yardley DA, et al. Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC).

2015;33(suppl; abstr 1003). meetinglibrary.asco.org/ record/109828/abstract.

Yardley DA, Weaver R, Melisko ME, et al. EMERGE: a randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer. 

 2015;33(14):1609-1619. doi: 10.1200/JCO.2014.56.2959.

Bardia A, Mayer IA, Diamond JR, et al. Efficacy and safety of Anti-Trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. 

 2017;35(19):2141-2148. doi: 10.1200/JCO.2016.70.8297.

Brufsky A, Miles D, Zvirbule Z, et al. Cobimetinib combined with paclitaxel as first-line treatment for patients with advanced triple-negative breast cancer (COLET study): Primary analysis of cohort I. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Poster P5-21-01. sabcs17.posterview.com/nosl/i/P5-21-01.

Kim SB, Dent R, Im SA, et al; LOTUS Investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. 

2017;18(10):1360-1372. doi: 10.1016/S1470-2045(17)30450-3.

Although chemotherapy remains the mainstay of treatment for patients with triple-negative breast cancer, promising developments are unfolding on several fronts, including new ways of using existing therapies and the exploration of immunotherapy, novel antibodies, and agents targeting the PI3K/mTOR/AKT pathway.

Jennifer W. Fink

Articles

HR-Positive Advances Highlight the Good News in Breast Cancer

Progress for TNBC Seen Across Treatment Modalities