The evolution of non-small cell lung cancer metastases in TRACERx

Breast Cancer Treatment: NCCN Guideline Updates And Optimism At ASCO 2024

In this episode of Managed Care Cast, Nihar Desai, MD, MPH, cardiologist and vice chief of Cardiology at the Yale School of Medicine, discusses therapies for cardiovascular conditions as they relate to patient adherence, polypharmacy, and health access.

NCCN Guidelines Recommend Capivasertib, Fulvestrant For Certain Patients With Breast Cancer

In a recent update, the National Comprehensive Cancer Network (NCCN) recommended capivasertib combined with fulvestrant for hormone receptor–positive and HER2-negative locally advanced or metastatic breast cancer, targeting patients with specific genetic mutations.

Patient with breast cancer approved for capivasertib combined with fulvestrant - Image Credit: Seventyfour - stock.Adobe.Com

The National Comprehensive Cancer Network (NCCN) Guidelines for breast cancer recently added capivasertib (Truqap) combined with fulvestrant (Faslodex) for patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer. The combination was first added as a category 1 recommendation—a preferred second or subsequent-line therapy in patients with PIK3CA or AKT1–activating mutations or PTEN alterations—in December 2023.1

The FDA approved capivasertib combined with fulvestrant for the treatment of adult patients with hormone receptor (HR)–positive, HER2-negative, locally advanced or metastatic breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations after progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy in November 2023.2 The agency's green light was based on results from the phase 3 CAPItello-291 trial (NCT04305496), in which capivasertib plus fulvestrant showed a median progression-free survival (PFS) of 7.3 months (95% CI, 5.5-9.0) vs 3.1 months (95% CI, 2.0-3.7) among patients treated with placebo plus fulvestrant.

This guideline update is significant because HR-positive breast cancer is the most common type of breast cancer, impacting more than half of the population diagnosed with breast cancer tumors.3PIK3CA, AKT1, and PTEN alterations frequently occur in HR-positive breast tumors, affecting up to half of patients with advanced HR-positive breast cancer.

CAPItello-291 was a double-blind, randomized trial that focused on the efficacy of capivasertib combined with fulvestrant (n = 355) compared with a placebo group (n = 353).4 Patients included in the experimental group were given 400 mg of capivasertib twice daily for 4 days on and 3 days off combined with 500 mg of fulvestrant for days 1 and 15, then 4 weeks following. Both the experimental (n = 155) and placebo (n = 134) cohorts had patients with AKT pathway-altered tumors.

The overall response rate was 22.9% among patients in the experimental cohort vs 12.2% for patients in the placebo group. Patients with an AKT pathway alteration had an overall response rate of 28.8% in the experimental group and 9.7% in the placebo cohort. Adverse events identified throughout the study were rash (12.1%), diarrhea (9.3%), and hyperglycemia (2.3%). These observations were consistent with data from earlier studies that tested capivasertib.

More recent updates to the NCCN breast cancer guidelines have included changing olaparib from a category 2A to a category 1 recommendation for those with HR-negative/HER2-negative and HR-positive/HER2-negative disease harboring BRCA1/2 mutation and residual disease after preoperative therapy in version 1.2024 of the guidelines.5 Another addition was the regimen of paclitaxel/carboplatin plus trastuzumab plus pertuzumab for patients with HER2-positive disease, which is a category 2A, or other recommended regimen.

In version 2.2024 of the guidelines, a footnote was added to relevant pages in the guidelines to note that a denosumab biosimilar is an appropriate substitute for denosumab.6 This change was in response to the FDA approval of biosimilars for denosumab in March 2024.6,7

The FDA also granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive solid tumors based on results from the DESTINY-PanTumor02 trial (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 trial (NCT04744831).8 Fam-trastuzumab deruxtecan-nxki is currently a preferred category 1 second-line therapy for HR-positive/HER2-negative breast cancer with visceral crisis or endocrine refractory, triple-negative breast cancer with no germline BRCA1/2 mutation, and in second-line HR-positive or HR-negative and HER2-positive breast cancer.6

References

1. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 5.2023. Accessed June 12, 2024. Https://www.Nccn.Org/guidelines/guidelines-process/transparency-process-and-recommendations

2. Ryan C. FDA approves capivasertib plus fulvestrant in advanced HR+/HER2– breast cancer with PIK3CA, AKT1, or PTEN alterations. AJMC®. November 20, 2023. Accessed June 12, 2024. Https://www.Ajmc.Com/view/fda-approves-capivasertib-plus-fulvestrant-in-advanced-hr-her2-breast-cancer-with-pik3ca-akt1-or-pten-alterations

3. ‌Truqap (capivasertib) plus Faslodex approved in the US for patients with advanced HR-positive breast cancer. Press release. AstraZeneca; November 17, 2023. Accessed June 5, 2024. Https://www.Astrazeneca.Com/media-centre/press-releases/2023/truqap-approved-in-us-for-hr-plus-breast-cancer.Html#!

4. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor-positive advanced breastcancer. N Engl J Med. 2023;388(22):2058-2070. Doi:10.1056/NEJMoa2214131

5. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 1.2024. Accessed June 12, 2024. Https://www.Nccn.Org/guidelines/guidelines-process/transparency-process-and-recommendations

6. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 2.2024. Accessed June 12, 2024. Https://www.Nccn.Org/professionals/physician_gls/pdf/breast.Pdf

7. Joszt L. FDA approves first 2 denosumab biosimilars. AJMC®. March 5, 2024. Accessed June 12, 2024. Https://www.Ajmc.Com/view/fda-approves-first-2-denosumab-biosimilars

8. Joszt L. Trastuzumab deruxtecan receives FDA approval for HER2-rositive solid tumors. AJMC®. April 5, 2024. Accessed June 12, 2024. Https://www.Ajmc.Com/view/trastuzumab-deruxtecan-receives-fda-approval-for-her2-positive-solid-tumors

Expert Breast Cancer Treatment Recommendations Based On Latest Evidence

PLYMOUTH MEETING, October 5. /PRNewswire/. During Breast Cancer Awareness Month this October, the National Comprehensive Cancer Network® (NCCN®) is sharing and updating evidence- and expert consensus-based management recommendations which lead to optimal outcomes for people with breast cancer.1 Translations of the English-language NCCN Guidelines® for Breast Cancer have recently been updated in Chinese, Japanese, and Spanish. The currently-available Korean, French, Polish, and Portuguese versions will be updated by the end of the month. All are free at NCCN.Org/global.

"Breast cancer has a very high cure rate, but remains the most common cancer and the leading cause of cancer-related death for women worldwide," said Robert W. Carlson, MD, Chief Executive Officer, NCCN and Professor of Medicine (Emeritus), Stanford University Medical Center, who specialized in breast cancer. "We want health care providers everywhere to have access to the carefully-vetted treatment recommendations included in the NCCN Guidelines. That's why we're always looking for ways to increase the readability and accessibility of these resources."

NCCN also adapts NCCN Guidelines into tiered and pragmatic approaches for varying resource availability in low- and middle-income countries, called the NCCN Framework for Resource Stratification of NCCN Guidelines (NCCN Framework™). There are also International Adaptations of the NCCN Guidelines for Breast Cancer for the Middle East and North Africa (MENA) region and Spain, as well as NCCN Harmonized GuidelinesTM for Sub-Saharan Africa and the Caribbean, all written in collaboration with regional oncology experts.

The NCCN Guidelines for Breast Cancer have also served as the basis for creation of three volumes of NCCN Guidelines for Patients®, to help cancer patients talk with their physicians about the best treatment options for Ductal Carcinoma in Situ (DCIS), Invasive Breast Cancer, and Metastatic Breast Cancer.

"We are expanding our knowledge of this disease at a rapid pace," said William J. Gradishar, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chair, NCCN Guidelines Panel for Breast Cancer. "We've made six updates to the main breast cancer guidelines already this year. They include multiple new treatment recommendations covering management, staging, and special circumstances such as pregnancy."

NCCN also has separate guidelines on topics like screening, genetic/familial risk assessment, risk reduction, and supportive care.

The NCCN Guidelines for Breast Cancer were downloaded more than 890,000 times in 2019, making it the most-downloaded NCCN guideline across all cancer types. At least 335,000 of those downloads came from outside the United States, including more than 36,000 from Spain and Mexico, 31,000 from China, and 21,000 from Brazil. The non-English versions were downloaded more than 4,000 times.

Visit NCCN.Org/global to learn more about all of the available cancer resources, and join the conversation with the hashtag #NCCNGlobal.

Free Breast Cancer Patient Webinars

The NCCN Foundation® is hosting two free patient webinars about metastatic breast cancer on October 8 and 12, 2020, based on the NCCN Guidelines for Patients.

Visit nccn.Org/patients/resources/breast-cancer-2020.Aspx for more information and registration.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network® (NCCN®) is a not-for-profit alliance of leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, efficient, and accessible cancer care so patients can live better lives. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) provide transparent, evidence-based, expert consensus recommendations for cancer treatment, prevention, and supportive services; they are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine. The NCCN Guidelines for Patients® provide expert cancer treatment information to inform and empower patients and caregivers, through support from the NCCN Foundation®. NCCN also advances continuing education, global initiatives, policy, and researchcollaboration and publication in oncology. Visit NCCN.Org for more information and follow NCCN on Facebook @NCCNorg, Instagram @NCCNorg, and Twitter @NCCN.

Media Contact:Rachel Darwin267-622-6624darwin@nccn.Org

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