BREAST CANCER

Three clinical trials presented at the 2019 ESMO Congress show that the tropomyosin receptor kinase inhibitor larotrectinib continues to show anti-tumor activity, including long-lasting objective responses and low toxicity, according to results from an integrated analysis.

Results from the phase III MONARCH 2 trial showed that the addition of the CDK4/6 inhibitor abemaciclib to fulvestrant improved overall survival by 9.4 months compared with fulvestrant and placebo in patients with hormone receptor–positive, HER2-negative advanced breast cancer who progressed on prior endocrine therapy, according to data presented at the 2019 ESMO Congress.

A subgroup of patients with triple-negative breast cancer who had immune cell PD-L1 expression, by the SP142 immunohistochemistry assay had responses to atezolizumab and nab-paclitaxel, regardless of whether they had primary or metastatic disease, according to an exploratory biomarker substudy of IMpassion130.

Patients with advanced hormone receptor–positive, HER2-positive breast cancer had improved progression-free survival when receiving the CDK4/6 inhibitor abemaciclib and endocrine therapy with trastuzumab compared with trastuzumab and chemotherapy, according to findings from the randomized phase II monarcHER trial.¹

Ribociclib with fulvestrant resulted in a clinically significant overall survival benefit compared with placebo in postmenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer, according to findings from the phase III MONALEESA-3 trial presented at the 2019 ESMO Congress.

Patients with early triple-negative breast cancer receiving neoadjuvant treatment with the combination of pembrolizumab and chemotherapy showed extended pathological complete response rates by 13.6 percentage points compared with chemotherapy alone in the phase III KEYNOTE-522 study.

A randomized phase II study with patients with metastatic triple-negative breast cancer showed unexpected improved overall survival with the addition of trilaciclib, an investigational CDK4/6 inhibitor, to gemcitabine and cisplatin, even though the combination failed to meet a safety-related primary endpoint.

The addition of atezolizumab to ado-trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive advanced breast cancer compared with T-DM1 alone, according to a second OS analysis of the phase II KATE2 trial presented at the 2019 ESMO Congress.

The phase III FeDeriCa trial found that a fixed-dose subcutaneous injection of pertuzumab and trastuzumab with hyaluronidase in combination with intravenous chemotherapy was pharmacokinetically noninferior&nbsp;to the standard IV infusions of the regimen in patients with HER2-positive breast cancer.<br /> &nbsp;

The FDA has issued a warning for a rare, but severe, lung inflammation that could be caused by the use of CDK4/6 inhibition in patients with advanced breast cancers.&nbsp;The warning applies to treatment with palbociclib, ribociclib, and abemaciclib specifically, but warnings of the risk of lung inflammation have been approved to be added to the prescribing information for the entire class of CDK4/6 inhibitors.

In an interview with Targeted Oncology, Charles Geyer, MD,&nbsp;discussed the potential role of neratinib as well as other new agents that are coming down the pipeline for the treatment of patients with metastatic HER2-positive breast cancer. He also addressed the biggest challenges oncologists face in managing this disease.

The FDA has accepted a supplemental New Drug Application for the use of neratinib in combination with capecitabine for the treatment of patients with HER2-positive metastatic breast cancer following failure of &ge;2 prior lines of HER2-directed therapy.

In an interview with&nbsp;Targeted Oncology, John Bartlett, MD, explained the standardized cancer testing project, its relevance, and how it could be used to improve the treatment of patients with pancreatic, prostate, breast cancer.&nbsp;

In an interview with&nbsp;Targeted Oncology, Muhammed Murtaza, MBBS, PhD, discussed the role for TARDIS in the treatment landscape of early-stage breast cancer, as well as the data supporting its use. He also highlighted next steps necessary for validating these results and the potential clinical value of liquid biopsies in the breast cancer space.

Jesus Anampa, MD, MS, assistant professor, Department of Medicine, Albert Einstein School of Medicine, says in the past, most patients with breast cancer were treated with chemotherapy. In some cases, these patients were being over-treated. To limit the use of chemotherapy in patients who don&rsquo;t need it, a group of researchers conducted the TAILORx trial.

The United States Preventive Services Task Force is recommending that therapies like tamoxifen, raloxifene, or aromatase inhibitors be administered to women who have a high risk for developing breast cancer and low risk for the adverse events that may be caused by these therapies. This recommendation is part of an update to the USPSTF recommendation statement on treatments for reducing breast cancer risk.

Angela DeMichele, MD, MSCE, discusses predictors of response to neoadjuvant chemotherapy in various subgroups of patients with breast cancer. Selecting characteristics of patients who will most likely benefit from this therapy is not an exact science, she adds.

The FDA has granted neratinib with an orphan drug designation for the treatment of patients with breast cancer&ndash;related brain metastases.

The combination of atezolizumab and nab-paclitaxel has been approved by the European Commission as a frontline treatment for adult patients with unresectable, locally advanced, or metastatic PD-L1&ndash;positive triple-negative breast cancer, a result of the positive outcomes in the phase III IMpassion130 trial.

The FDA has drafted new industry recommendations for sponsors to encourage male inclusion in clinical trials for breast cancer.<br /> &nbsp;

In an interview with <em>Targeted Oncology,</em> Carol Mangione, MD, MSPH, a co-author on the USPSTF Recommendation Statement, gave insight&nbsp;into the specifics of the recommendations and how the Task Force hopes these suggestions will impact patient outcomes.<br /> &nbsp;

CDK4/6 inhibitors<strong> </strong>offer clear benefits in pro&shy;gression-free survival, delayed time to chemotherapy, and overall survival in both pre and postmenopausal patients with estrogen receptor-positive metastatic breast cancer, said Angela DeMichele, MD, MSCE.

In a presentation at the <em>18th Annual </em>International Congress on the Future of Breast Cancer&reg; East, hosted by Physicians&rsquo; Education Resource&reg;, LLC, in New York, Armin Shahrokni, MD, MPH, emphasized the importance of performing a comprehensive geriatric assessment for each patient to determine optimal treatment.

The American Society of Clinical Oncology and Friends of Cancer Research have issued a joint research statement that broadens eligibility criteria affecting 2 patient subgroups: patients with treated/stable brain metastases and those with new, active, or progressive brain metastases.<br /> &nbsp;

Both cell cycle-specific and nonspecific mechanisms that lead to acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer have resulted in multiple promising agents and combinations for the second-line management of metastatic disease.