The National Institute for Health and Care Excellence has published draft guidance that recommends fam-trastuzumab deruxtecan-nxki for the treatment of patients with unresectable or metastatic HER2-positive breast cancer following 2 or more anti-HER2 therapies.
The National Institute for Health and Care Excellence (NICE) has published draft guidance that recommends fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with unresectable or metastatic HER2-positive breast cancer following 2 or more anti-HER2 therapies.1 The treatment is now recommended for use within the Cancer Drugs Fund (CDF).
In the final appraisal document, NICE stated that the recommendation is not intended to affect trastuzumab deruxtecan treatment that begin in the National Health Service (NHS) prior to the guidance being published. Those receiving this treatment outside of the recommendation can continue without change “to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.”
NICE did note that the final data from the DESTINY-Breast01 trial—the basis for the decision—are not yet available, and because of this, the estimates of cost effectiveness for the antibody-drug conjugate (ADC) are uncertain. Therefore, trastuzumab deruxtecan cannot yet be recommended for routine use in the NHS.
The list price by the manufacturers, which are Daiichi Sankyo and AstraZeneca, is £1455 ($2012.45) per vial, which contains 100 mg powder for concentrate for solution for infusion. Moreover, the average cost of a treatment course at list price is £118,000 (~$164,021).
“Trastuzumab deruxtecan could be cost effective if further data shows that people live longer with treatment,” the agency noted in the final appraisal document. “Another ongoing trial is directly comparing trastuzumab deruxtecan with anti-HER2 therapies plus chemotherapy. Data from the trials of trastuzumab deruxtecan and from NHS practice would help address the uncertainty about clinical effectiveness. Trastuzumab deruxtecan is therefore recommended for use in the Cancer Drugs Fund.”
The FDA approved trastuzumab-deruxtecan in December 2019 for use in adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more previous anti–HER2-based regimens in the metastatic setting. The approval was based on previous data from the phase 2 DESTINY-Breast01 study.
The clinical evidence for the NICE decision was based on single-arm data from DESTINY-Breast01, in which trastuzumab deruxtecan demonstrated clinically meaningful and durable anticancer activity in patients with HER2-positive metastatic breast cancer who had received 2 or more prior HER2-based therapies.2
The open-label, international, multicenter, phase 2 DESTINY-Breast01 trial enrolled 184 heavily pretreated patients with HER2-positive breast cancer; these patients had received ado-trastuzumab emtansine (T-DM1; Kadcyla) and other HER2-targeted agents. In part 1 of the trial, investigators evaluated the pharmacokinetics of the agent in 65 patients and set out to identify the recommended phase 2 dose (RP2D; n = 25). The RP2D of the ADC was 5.4 mg/kg.
To be eligible for enrollment, patients had to be at least 18 years of age, have unresectable and/or metastatic breast cancer, HER2 positivity, and have previously received T-DM1. Those who had a history of significant interstitial lung disease were not included. However, those with stable, treated brain metastases were permitted.
The primary end point was objective response rate (ORR) per independent central review, while secondary end points comprised disease control rate, duration of response (DOR), and progression-free survival (PFS).
All patients were female, and the median age was 55 years; 55% were white and 38% were Asian. Fifty-three percent of patients had hormone receptor–positive disease, while 45% were HR negative. The median number of previous treatment regimens received at baseline was 6 (range, 2-27); these treatments included trastuzumab (Herceptin; 100%), T-DM1 (100%), pertuzumab (Perjeta; 65.8%), other HER2-targeted antibodies or ADCs (6.0%), other HER2-targeted TKIs (50.5%), hormonal treatment (48.9%), and other previous systemic therapy (99.5%).
At a median follow-up of 20.5 months, 20.1% of patients were still on treatment. Just under half, or 43.4% of patients were on treatment for longer than 1 year and 6.0% continued on the ADC for over 2 years. With increased maturity of the data DORs increased, 65.2% of participants were censored.
At a median follow-up of 20.5 months, the ADC elicited a confirmed ORR of 61.4% (95% CI, 54.0%-68.5%); this comprised a complete response rate of 6.5%, a partial response rate of 54.9%, and a stable disease rate of 35.9%. Moreover, 1.9% of patients experienced disease progression. The median DOR with trastuzumab deruxtecan was 20.8 months.
Additional findings that were presented during the 2020 San Antonio Breast Cancer Symposium showed that the estimated 1-year OS rate was 85% (95% CI, 79%-90%); the estimated OS rate at 18 months was 74% (95% CI, 67%-80%). Moreover, the median PFS was 19.4 months (95% CI, 14.1–not estimable [NE]). Although still immature, the preliminary median OS with the agent was 24.6 months (95% CI, 23.1-NE).
A pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who were given at least 1 dose of the ADC at 5.4 mg/kg in trials showed that the most frequently reported toxicities included nausea (79.9%), fatigue (60.3%), vomiting (48.7%), alopecia (46.2%), constipation (35.9%), reduced appetite (34.6%), anemia (33.8%), neutropenia (32.5%), diarrhea (30.8%), thrombocytopenia (23.1%), cough (21.4%), leukopenia (20.5%), and headache (20.1%).