Efficacy

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ExteNET is a large trial designed to investigate the efficacy of extended adjuvant NERLYNX after trastuzumab-based therapy in HER2+ early breast cancer

ExteNET study is a randomised phase III trial evaluating the addition of 1 year of NERLYNX after trastuzumab therapy in HER2+ early breast cancer.^#,1-4 Patients were treated with chemotherapy and trastuzumab. At the time of the ExteNET trial patient recruitment, pertuzumab and trastuzumab emtansine (TDM-1) were not available for adjuvant treatment in HER2+ early breast cancer. Patients included in the ExteNET trial only received prior trastuzumab.¹

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CNS, central nervous system; DCIS, ductal carcinoma in situ; DFS, disease-free survival; EQ-5D, EuroQol5-Dimension Questionnaire; FACT-B, Functional Assessment of Cancer Therapy-Breast; HER2, human epidermal growth factor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridisation; T-DM1, trastuzumab emtansine.
#ExteNET is a double-blinded placebo-controlled study.
§Locally confirmed HER2 status (IHC 3+ or ISH).
*Patients were treated with chemotherapy and trastuzumab. Patient had not received treatment with T-DM1. Select exclusion criteria: clinically significant cardiac, GI or psychiatric comorbidities; inability to swallow pills.
†iDFS defined as the time between the date of randomisation to the first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distant recurrence or death from any cause, with 2 years and 28 days of follow-up.
‡Results of ExteNet study are supported by a descriptive analysis of 5-year follow-up, with 74.5% (2117/2840) of patients re-consented.

NERLYNX significantly improves invasive disease-free survival (iDFS) vs placebo in patients with HER2+ early breast cancer^2,3,5

ExteNET study met its primary endpoint and demonstrates the benefit of adding NERLYNX after a trastuzumab-based therapy for patients with HER2+ early breast cancer (ITT population, n=2840).⁵

iDFS after adjuvant therapy at 2 years: 94.2% vs 91.9% NERLYNX vs placebo; absolute benefit 2.3%.

33% relative reduction in the risk of disease recurrence* vs placebo in patients with HER2+ early breast cancer.⁵
HR: 0.67 (95% CI; 0.49-0.91); P=0.011⁵

See patient characteristics

CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; ITT, intention-to-treat; iDFS, invasive disease-free survival.
*“Recurrence” defined as the first occurrence of any of the following events: recurrence of ipsilateral invasive breast tumour, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence, or death from any cause at 2 years after randomisation.

NERLYNX shows superior benefit in patients with HER2+/HR+ early breast cancer who have completed trastuzumab-based therapy less than 1 year ago, granting marketing EU authorisation in this specific population^*†‡1,5

Invasive disease-free survival (iDFS) in HER2+/HR+ ≤ 1-year from completion of prior trastuzumab-based therapy population (n=1334)

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Graph adapted from Chan A, et al. Clin Breast Cancer 2021.

CI, confidence interval; EU, Europe; HER2+, human epidermal growth factor receptor 2 positive; HR, hazard ratio; HR+, hormone receptor positive; iDFS, invasive disease-free survival.
*Results of ExteNET are supported by a descriptive analysis of 5-year follow-up with 74.5% (2117/2840) of patients reconsented. 95% of the HER2+/HR+ study population received concurrent endocrine therapy. 5 years are the last updated results. iDFS results are expressed in Interactive Response Technology (IRT) based analysis.
†Recurrence is defined as an invasive disease event or death.
‡Unstratified.

See ExteNET final results publication

Some patients are at a heightened risk of recurrence^*1,6-8

Risk considerations in early-stage HER2+ breast cancer patients

• One or more positive nodes⁶

• Tumor diameter ≥ 2cm⁸

• Residual disease after neoadjuvant treatment^1,7,8

• High Ki-67^†

• HR-status¹

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Anna, pre-menopausal patient
with node-positive disease

Following surgery and adjuvant trastuzumab-based therapy together with endocrine therapy, Anna is disease-free

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Sofia, postmenopausal non-pCR patient 
following neoadjuvant treatment

Sofia has undergone a number of cycles of neoadjuvant therapy, surgery and adjuvant therapy

HR, hormone receptor; HER2, human epidermal growth factor receptor 2; pCR, pathological complete response.
*“Recurrence” defined as the first occurrence of any of the following events: recurrence of ipsilateral invasive breast tumour, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence, or death from any cause.
^†KI-67 high/low classification should be according to the centers' local standards.

NERLYNX can help reduce Anna’s risk of recurrence^*1,4,6

Anna Node-positive patient

For HER2+ node-positive patients, like Anna, the risk of recurrence increases with the number of lymph nodes involved:*

• 1-3 nodes involved: 25% relapse
• ≥4 nodes involved: 44% relapse

at 10 years following 1 year trastuzumab^*†6

Anna is HER2+/HR+ node-positive patient. Recurrence rates presented from HERA trial are according to node-positive status and without specified HR status.

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See ExteNET study results in the node positive subgroup of patients

CI, confidence interval; HR, hazard ratio; HER2, human epidermal growth actor receptor; HR+, hormone receptor positive.
Descriptive analysis from ExteNET study.
*“Recurrence” defined as the first occurrence of any of the following events: recurrence of ipsilateral invasive breast tumour, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence, or death from any cause.
†Dosage: once at 8 mg/kg body weight intravenously, then 6 mg/kg once every 3 weeks.
‡The ExteNET study enrolled a majority of patients that were node positive (1,079 out of 1,334 in the EU label population). This is from a forest plot of HER2+/HR+ ≤ 1 year from completion of trastuzumab-based treatment subgroup analysis from ExteNET study.

NERLYNX can help reduce Sofia’s risk of recurrence^*1,4,7

Sofia Non-pCR patient after neoadjuvant treatment

For patients like Sofia, who did NOT achieve a pCR and received trastuzumab-DM1, the risk of recurrence is:

• 9.3% at 3 years following 42 weeks of T-DM1^*†7

In descriptive analysis of patients who did not achieve a pCR after trastuzumab-based adjuvant therapy, NERLYNX demonstrates an absolute benefit vs placebo:^‡1,4

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See iDFS study results

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See DDFS study results

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See OS study results

In ExteNET study, patients were treated with trastuzumab, not with T-DM1 since T-DM1 was not available at that time.

CI, confidence interval; DDFS, distant disease-free survival; HR, hazard ratio; iDFS, invasive disease-free survival; NS, not significant; OS, overall survival; pCR, pathological complete response; T-DM1, trastuzumab emtansine.
Descriptive analysis from ExteNET study.
*“Recurrence” defined as the first occurrence of any of the following events: recurrence of ipsilateral invasive breast tumour, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence, or death from any cause.
†Dosage: Loading dose of 8 mg/kg body weight administered if more than 6 weeks had elapsed since preceding dose of trastuzumab, followed by 3.6 mg/kg body weight intravenously, once every 3 weeks for 14 cycles.
‡295 HER2+/HR+ patients who had residual disease after neoadjuvant treatment were included in the ExteNET study and received either NERLYNX or placebo.
 

See possible clinical scenarios