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The Scottish Medicines Consortium has accepted fam-trastuzumab deruxtecan-nxki as a treatment option for adult patients with HER2-positive unresectable or metastatic breast cancer who have previously received 2 or more anti–HER2-based therapies.
The Scottish Medicines Consortium (SMC) has accepted fam-trastuzumab deruxtecan-nxki (Enhertu) as a treatment option for adult patients with HER2-positive unresectable or metastatic breast cancer who have previously received 2 or more anti–HER2-based therapies.1
Specifically, the antibody-drug conjugate (ADC) was accepted for utilization on an interim basis that is subject to ongoing evaluation and future assessment, according to Daiichi Sankyo UK Ltd and AstraZeneca UK.
The SMC advice is supported by findings from an analysis of the phase 2 DESTINY-Breast01 trial (NCT03248492), which had a data cutoff date of June 2020.2 At a median follow-up of 20.5 months (range, 0.7-31.4), trastuzumab deruxtecan elicited a confirmed objective response rate (ORR) of 61.4% (95% CI, 54.0%-68.5%) in this patient population (n = 184); this included a complete response (CR) rate of 6.5% and a partial response (PR) rate of 54.9%.
Moreover, the median duration of response (DOR) was 20.8 months (95% CI, 15.0–not reached) with the ADC, with 81.5% of patients experiencing a response of at least 6 months (95% CI, 72.2%-88.0%).
“This acceptance is a significant milestone for the people in Scotland living with HER2-positive metastatic breast cancer,” Lesley Stephen, patient representative for METUP UK, stated in a press release. “There is a significant unmet need within metastatic breast cancer and new treatment options are important in tackling the disease burden.”
The multicenter, open-label, single-arm phase 2 trial enrolled patients with HER2-positive, unresectable and/or metastatic breast cancer who had previously received 2 or more anti–HER2-based regimens, which included ado-trastuzumab emtansine (Kadcyla; 100%), trastuzumab (Herceptin; 100%), and pertuzumab (Perjeta; 65.8%). Patients needed to have measurable disease per RECIST v1.1 criteria and archival breast tumor samples available to determine HER2 status.
If patients had a history of treated interstitial lung disease (ILD) or ILD at the time of screening, had untreated or symptomatic brain metastases, or a history of clinically significant cardiac disease, they were excluded.
Study participants were administered the ADC via an intravenous infusion at a dose of 5.4 mg/kg once every 3 weeks until progressive disease, withdrawn consent, or intolerable toxicity.
The primary end point of the trial was ORR per RECIST v1.1 criteria in the intent-to-treat population and per independent central review. A key secondary end point was DOR.
Among the 184 patients enrolled to the trial, the median age was 55 years (range, 28-96), and 23.9% of patients were aged 65 years or older. Moreover, 100% were female, 54.9% were White, 38.0% were Asian, and 2.2% were Black or African American. Additionally, 55.4% had an ECOG performance status of 0 and 44.0% had a status of 1.
Furthermore, 52.7% of patients had hormone receptor positivity, 91.8% had the presence of visceral disease, 13.0% had previously treated and stable brain metastases, and the median number of prior lines of treatment received was 5 (range, 2-17).
Data from an earlier analysis of the trial showed that at a median follow-up of 11.1 months (range, 0.7-19.9), the ADC induced an ORR of 60.9% (95% CI, 53.4%-68.0%), which included a CR rate of 6.0% and a PR rate of 54.9%. Moreover, 36.4% of patients had stable disease, 1.6% experienced disease progression, and 1.1% were not determined to be evaluable. At this time point, the median DOR with trastuzumab deruxtecan was 14.8 months (95% CI, 13.8-16.9), and 81.3% experienced responses that persisted for at least 6 months (95% CI, 71.9%-87.8%).
The ADC was found to have a tolerable toxicity profile, with 18.5% of patients discontinuing treatment because of treatment-emergent adverse effects.
The safety of trastuzumab deruxtecan was assessed in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who previously received at least 1 dose of the ADC at 5.4 mg/kg in clinical trials. The median duration of exposure to the drug was 9.8 months (range, 0.7-37.1).
The most frequent toxicities experienced with the ADC included nausea (79.9%), fatigue (60.3%), vomiting (48.7%), alopecia (46.2%), constipation (35.9%), decreased 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%). Fifteen percent of patients reported ILD or pneumonitis. Three percent of patients experienced fatal outcomes.
“We are pleased with the SMC’s decision to publish acceptance of this treatment,” Haran Maheson, commercial director for Oncology at Daiichi Sankyo UK, added in the release. “Trastuzumab deruxtecan is now available within its licensed indication across Great Britain and we’ll work hard to support clinicians in their efforts to improve the quality of care to patients.”
In December 2019, the FDA granted an accelerated approval to trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who previously received 2 or more lines of anti–HER2-based regimens in the metastatic setting.3 The decision was supported by earlier data from DESTINY-Breast01.
In April 2021, the National Institute for Health and Care Excellence recommended trastuzumab deruxtecan for the treatment of patients with unresectable or metastatic HER2-positive breast cancer following 2 or more anti-HER2 therapies.4 The ADC was also accepted for use in Wales, in line with the recommendation.
Regulatory discussions with North Irish health authorities are ongoing.