Efficacy

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ExteNET is a large phase III trial designed to investigate the efficacy of neratinib as an extended adjuvant treatment post 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 in HER2+ early breast cancer.^1-4 Patients were treated with chemotherapy and trastuzumab. At the time of the ExteNET trial patient recruitment, trastuzumab emtansine (TDM-1) was not licensed or available for adjuvant treatment in early breast cancer therefore 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.
*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.
†Invasive disease-free survival (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 an exploratory 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 the ITT population^2,3,5

ExteNET study met its primary endpoint and demonstrated the benefit of adding NERLYNX after a trastuzumab-based therapy for HER2+ early breast cancer patients.⁵

Primary endpoint presented in the Summary of Product Characteristics (SmPC) is the 2-year data in ITT population, iDFS after adjuvant therapy at 2 years: 94.2% vs 91.9% NERLYNX vs placebo; absolute benefit 2.3%.

33% reduction of the relative risk of disease recurrence vs placebo in the ITT population^*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.
*“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 HER2+/HR+ early breast cancer patients who have completed trastuzumab-based therapy less than 1 year ago, granting marketing autorisation in this specific population^*†‡1,5

Invasive disease-free survival (iDFS) in HER2+/HR+ <1 year from completion of prior trastuzumab-based therapy population:

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

CI, confidence interval; HER2+, human epidermal growth factor receptor 2 positive; HR, hazard ratio; HR+, hormone receptor positive; iDFS, invasive disease-free survival
*NERLYNX EU label population: HER2+/HR+ patients completing prior trastuzumab-based treatment ≤1 year from randomisation. 5 years are the last updated results. Results of ExteNET are supported by an exploratory 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. 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^1,7,8

• High Ki-67

• High BMI

• Medium/High grading

• Younger age

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Anna, pre-menopausal patient
with node-positive disease

Anna is disease-free, following surgery, adjuvant trastuzumab-based therapy and hormone therapy.

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Sofia, post-menopausal patient
with no pCR following neoadjuvant treatment

Sofia has undergone a number of cycles of neoadjuvant therapy, surgery and adjuvant therapy, and is currently disease-free

BMI, body mass index; 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.

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+ and results presented from HERA trial are on HER2+ (HR status not specified, data not available).

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See ExteNET study results in the node positive subgroup of patients

CI, confidence interval; HR, hazard ratio; iDFS, invasive disease-free survival; OS, overall 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.
†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). NERLYNX showed a significant positive impact on N+ patient subgroup in iDFS with a reduction in the risk of recurrence of 40% at 5 years.

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

Sofia No pCR patient after neoadjuvant treatment

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

• 11,7% at 3 years following 42 weeks of T-DM1^*†7

Sofia is HER2+/HR+ and results presented from KATHERINE trial are on HER2+ (HR status not specified).
 

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

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See iDFS study results

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See OS study results

CI, confidence interval; HR, hazard ratio; iDFS, invasive disease-free survival; NS, not significant; OS, overall survival; pCR, pathological complete response; T-DM1, trastuzumab emtansine. *“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. In this exploratory subset analysis, NERLYNX showed 7.4% absolute benefit in iDFS at 5 years and 9.1% absolute benefit in overall survival at 8 years.