BREAST CANCER

The triplet combination of abemaciclib, trastuzumab, and fulvestrant showed a significant statistical improvement in progression-free survival compared with chemotherapy and trastuzumab in patients with heavily pretreated, hormone receptor–positive, HER2-positive breast cancer, according to the results of the phase II monarcHER trial.

The FDA has accepted and granted a priority review to a biologics license application for [fam-] trastuzumab deruxtecan (DS-8201) for the treatment of patients with HER2-positive metastatic breast cancer.

A phase III trial, HER2CLIMB-02, has been initiated to investigate the combination of tucatinib and ado-trastuzumab emtansine in patients with locally advanced or metastatic HER2-positive breast cancer. The results of the trial will support registration for tucatinib in the United States.

A greater understanding of the mechanisms underlying endocrine resistance, along with the development of targeted agents directed at key regulatory oncogenic pathways, continue to lead to new options in the treatment of hormone receptor–positive, HER2-negative breast cancer. These therapies offer the promise of better disease control rates and improved quality of life for patients with advanced disease.

Following the 2019 ESMO Congress, experts across various fields highlighted some next steps and how these treatment options will improve the treatment landscape for patients with ovarian, lung, breast, GI, or GU cancers. Overall, the abstracts presented at this year’s meeting will change the treatment paradigm in a number of patient populations.

The introduction of<strong> </strong>CDK4/6 inhibitors for the treatment of hormone receptor&ndash;positive, HER2-negative breast cancer has transformed therapy management and extended survival for this patient population. The next step in the process of tailoring therapy towards individual patients is the introduction of targeted therapies for patient subsets with driver aberrations.

The addition of direct oral oral anticoagulants for the management of venous thromboembolism in patients with cancer is the latest change to previous guidelines issued by the American Society of Clinical Oncology.

Cynthia X. Ma, MD, PhD discusses the challenges with understanding treatment duration for adjuvant endocrine therapy in patients with breast cancer.

The approval of alpelisib in May 2019 poses a challenge to oncologists and their practices with the emergence of hyperglycemia as an AE associated with PI3K inhibitors. Managing the patient effectively requires a multidisciplinary team approach that involves counseling up front, monitoring throughout the course of therapy, and input and feedback from the team of oncologists, advanced practice providers, pharmacists, and dietitians.

Using a measure known as the growth modulation index, patients with TRK fusion&ndash;positive cancers who were treated with larotrectinib had a clinically meaningful improvement in progression-free survival compared with the time to progression on their prior treatment, an analysis of patients enrolled in 1 of 3 clinical trials has found.

The FDA has approved a labeling supplement for neratinib for the extended adjuvant treatment of patients with HER2-positive early-stage breast cancer. The labeling supplement adds safety information based on interim findings from the phase II CONTROL trial, which investigated the use of preventive strategies to reduce the incidence and severity of neratinib-associated diarrhea.

George Sledge, Jr., MD, discusses the overall survival data of the phase III MONARCH-2 trial in advanced hormone receptor-positive, HER2-negative breast cancer.

CDK4/6 inhibitor&nbsp;abemaciclib plus endocrine therapy led to significant benefits in a population of predominantly Chinese women with advanced&nbsp;hormone receptor&ndash;positive/HER2-negative breast cancer, according to data from 2 randomized trials presented at the 2019 ESMO Congress.

Three clinical trials presented at the 2019 ESMO Congress show that the tropomyosin receptor kinase&nbsp;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&ndash;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&ndash;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&ndash;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.