Disease Analysis: HR+/HER2- Breast Cancer
Author: Tara Hansen
Publisher: Datamonitor Healthcare
- Description
- Contents
- Enquire
Latest key takeaways
- Human epidermal growth factor 2-positive (HER2+) breast cancer is characterized by amplification of the HER2/neu oncogene. Datamonitor Healthcare estimates that in 2018, there were 2.1 million incident cases and 8.6 million five-year prevalent cases of breast cancer worldwide. By 2027, incident and five-year prevalent cases of breast cancer are expected to increase to 2.3 million and 9.3 million cases, respectively.
- The market for drugs for HER2+ breast cancer will experience steady growth over the next 10 years across the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK). The primary drivers for this growth are the rising disease prevalence as well as the approval and subsequent uptake of new targeted therapies. The market for HER2+ breast cancer is also becoming increasingly crowded, creating fierce competition among approved and pipeline therapies.
- High prices for combination regimens will translate to high revenues, despite the introduction of trastuzumab biosimilars. The increased use of combination regimens, in conjunction with the continued uptake of other branded therapies and rising disease prevalence, will offset the decrease in revenues caused by these biosimilars.
- Herceptin is the current standard-of-care therapy, and is used in every line of treatment, primarily as part of a combination regimen. However, it is forecast to steadily lose market share following the introduction of trastuzumab biosimilars in 2019.
- Since its approval in 2013, Kadcyla has become the standard of care both for HER2+ breast cancer patients who have residual invasive disease after neoadjuvant taxane- and Herceptin-based treatment, and for patients with metastatic disease who have progressed on a trastuzumab-containing regimen.
- Despite initially encountering reimbursement challenges, Perjeta in combination with Herceptin has become the standard of care for both neoadjuvant and first-line treatment of HER2+ breast cancer after demonstrating an overall survival benefit in the Phase III CLEOPATRA and APHINITY studies.
- Nerlynx, which is approved for the extended adjuvant setting, has experienced limited commercial success due to a lack of an overall survival benefit, high rates of diarrhea, and high prices. Although Puma Biotechnology is positioning Nerlynx as a third-line treatment, the drug may struggle to gain market share in the increasingly crowded third-line market.
- Tykerb’s unfavorable clinical results and the success of Kadcyla in later lines of therapy have limited the tyrosine kinase inhibitor’s (TKI’s) commercial potential. The introduction of Enhertu and other expected third-line treatments will further limit Tykerb’s future commercial potential.
- Enhertu received accelerated approval in the US as a third-line treatment for locally advanced or metastatic patients after demonstrating strong efficacy results in the pivotal Phase II DESTINY-Breast01 study. Enhertu is currently being tested against investigator’s choice of treatment in the confirmatory Phase III DESTINY-Breast02 study. Daiichi Sankyo and AstraZeneca are also testing Enhertu in a head-to-head trial against Kadcyla in the Phase III DESTINY-Breast03 study, which could support a label expansion for Enhertu as a second-line treatment.
- Tukysa, which was recently approved in the US, will likely be the treatment of choice in third-line patients with brain metastases after demonstrating positive efficacy results in the pivotal Phase II HER2CLIMB study. However, Tukysa’s overall commercial potential will be limited by the small size of the heavily pretreated patient population with brain metastases.
- Margetuximab is also under regulatory review for this setting, but has a limited commercial outlook given it will face significant competition from both approved and late-phase competitors in an increasingly crowded market. Although margetuximab demonstrated a progression-free survival benefit and a trend toward an overall survival benefit in the Phase III SOPHIA study, both Tukysa and Enhertu have shown better efficacy results.
- The $6.9bn agreement signed in March 2019 between AstraZeneca and Daiichi Sankyo regarding the development and commercialization of Enhertu is the largest deal for a breast cancer therapy.
- Key recent events include pivotal trial read-outs, such as Kadcyla’s failure as an adjuvant therapy in combination with Perjeta in the Phase III KAITLIN study, as well as Tukysa’s Phase II success as a third-line therapy in HER2CLIMB. Key recent regulatory events include the US approval of Tukysa.
- Key upcoming catalysts for 2020 include the anticipated US approvals of margetuximab and the Perjeta/Herceptin subcutaneous fixed-dose combination. Additionally, results from the registrational Phase III TULIP study of (vic-)trastuzumab duocarmazine are also expected in 2020.
- The overall likelihood of approval of a Phase I breast cancer asset is 8.7%, and the average probability a drug advances from Phase III is 58.8%. Breast cancer drugs, on average, take 9.8 years from Phase I to approval, compared to 9.3 years in the overall oncology space.
CONTENTS
8 OVERVIEW
8 Latest key takeaways
10 DISEASE BACKGROUND
10 Definition
10 Risk factors
12 Symptoms
12 Diagnosis
12 Determination of HER2 status
13 Patient segmentation
14 TREATMENT
14 Referral patterns
14 Operable Stage I–III HER2+ breast cancer
14 Inoperable Stage III HER2+ breast cancer
14 Neoadjuvant/adjuvant therapy regimens
15 Treatment guidelines for Stage IV or recurrent HER2+ breast cancer
18 EPIDEMIOLOGY
21 Breast cancer subtypes
23 MARKETED DRUGS
30 PIPELINE DRUGS
43 KEY REGULATORY EVENTS
43 England’s NICE Says Yes To Kadcyla In Early Breast Cancer
43 Seattle Genetics Wins Early US FDA Approval For Tukysa, Plans Rapid Launch
43 Japan Enhertu Nod Another Boost For Daiichi’s Oncology Hopes
43 Ide-Cel and Enhertu Sponsors Keep Fingers Crossed For EMA Fast-Track
44 India’s SPARC Keeps Paclitaxel Ambition Burning For Now
44 Assessment Aid Speeds FDA Review Of Nerlynx In Third-Line Breast Cancer
44 Seattle Genetics’ Tucatinib Moves Quickly From BTD To NDA
44 Enhertu Earns Second-Fastest Review Time Of 2019
45 First Filing, In Japan, For Daiichi’s Lead ADC As Others Progress
45 FDA Approves Amgen And Allergan’s Kanjinti Trastuzumab Biosimilar
46 PROBABILITY OF SUCCESS
47 CLINICAL TRIAL LANDSCAPE
48 Sponsors by status
49 Sponsors by phase
50 Recent events
52 DRUG ASSESSMENT MODEL
54 MARKET DYNAMICS
55 FUTURE TRENDS
55 Launches of new targeted therapies and label expansions will drive growth in the HER2+ breast cancer market over the
forecast period
55 Uptake of combination regimens will drive high revenues
55 Pipeline drugs will face strong competition in a saturated market
56 Trastuzumab biosimilars will have a minor impact on the overall market
57 CONSENSUS FORECASTS
62 RECENT EVENTS AND ANALYST OPINION
62 Tukysa for Breast Cancer (May 29, 2020)
63 Kadcyla for Breast Cancer (May 13, 2020)
65 Onzeald for Breast Cancer (February 27, 2020)
66 Leronlimab for Breast Cancer (January 31, 2020)
67 Oral Paclitaxel for Breast Cancer (December 13, 2019)
68 Perjeta/Herceptin SQ FDC for Breast Cancer (December 12, 2019)
68 Enhertu for Breast Cancer (December 11, 2019)
70 Tukysa for Breast Cancer (December 11, 2019)
71 MCLA-128 for Breast Cancer (October 23, 2019)
72 Margetuximab for Breast Cancer (October 22, 2019)
74 Tukysa for Breast Cancer (October 21, 2019)
75 Verzenio for Breast Cancer (September 28, 2019)
77 Oral Paclitaxel for Breast Cancer (August 7, 2019)
78 Multiple Drugs for Breast Cancer (June 25, 2019)
79 Margetuximab for Breast Cancer (June 4, 2019)
80 Nerlynx for Breast Cancer (June 4, 2019)
82 Perjeta for Breast Cancer (June 2, 2019)
84 KEY UPCOMING EVENTS
86 KEY OPINION LEADER INSIGHTS
87 UNMET NEEDS
88 BIBLIOGRAPHY
89 Prescription information
91 APPENDIX
LIST OF FIGURES
13 Figure 1: Staging of HER2+ breast cancer
20 Figure 2: Trends in incident cases of breast cancer, 2018–27
30 Figure 3: Overview of pipeline drugs for breast cancer in the US
30 Figure 4: Pipeline drugs for breast cancer, by company
31 Figure 5: Pipeline drugs for breast cancer, by drug type
31 Figure 6: Pipeline drugs for breast cancer, by classification
46 Figure 7: Probability of success in the breast cancer pipeline
47 Figure 8: Clinical trials in breast cancer
47 Figure 9: Top 10 drugs for clinical trials in breast cancer
48 Figure 10: Top 10 companies for clinical trials in breast cancer
48 Figure 11: Trial locations in breast cancer
49 Figure 12: Breast cancer trials status
50 Figure 13: Breast cancer trials sponsors, by phase
52 Figure 14: Datamonitor Healthcare’s drug assessment summary for HER2+ breast cancer
54 Figure 15: Market dynamics for HER2+ breast cancer
55 Figure 16: Future trends in HER2+ breast cancer
63 Figure 17: Tukysa for Breast Cancer (May 29, 2020): Phase II – HER2CLIMB
65 Figure 18: Kadcyla for Breast Cancer (May 13, 2020): Phase III – KAITLIN (w/Perjeta, HER2+)
70 Figure 19: Enhertu for Breast Cancer (December 11, 2019): Phase II – DESTINY-Breast01 (HER2+)
74 Figure 20: Margetuximab for Breast Cancer (October 22, 2019): Phase III – SOPHIA (HER2+)
75 Figure 21: Tukysa for Breast Cancer (October 21, 2019): Phase II – HER2CLIMB
77 Figure 22: Verzenio for Breast Cancer (September 28, 2019): Phase II – monarcHER
78 Figure 23: Oral Paclitaxel for Breast Cancer (August 7, 2019): Phase III – KX-ORAX-001 (S. America)
80 Figure 24: Margetuximab for Breast Cancer (June 4, 2019): Phase III – SOPHIA (HER2+)
82 Figure 25: Nerlynx for Breast Cancer (June 4, 2019): Phase III – NALA – w/Xeloda vs. Tykerb/Xeloda (HER2+)
83 Figure 26: Perjeta for Breast Cancer (June 2, 2019): Phase III – CLEOPATRA
84 Figure 27: Key upcoming events in breast cancer (one of two)
85 Figure 28: Key upcoming events in breast cancer (two of two)
87 Figure 29: Unmet needs in HER2+ breast cancer
LIST OF TABLES
17 Table 1: Preferred branded treatments for HER2+ breast cancer
19 Table 2: Incident cases of breast cancer, 2018–27
21 Table 3: Five-year prevalent cases of breast cancer, 2018–27
22 Table 4: Breast cancer subtypes
24 Table 5: Marketed drugs for HER2+ breast cancer
32 Table 6: Pipeline drugs for HER2+ breast cancer in the US
58 Table 7: Historical global sales, by drug ($m), 2015–19
60 Table 8: Forecasted global sales, by drug ($m), 2020–24
62 Table 9: Tukysa for Breast Cancer (May 29, 2020)
64 Table 10: Kadcyla for Breast Cancer (May 13, 2020)
65 Table 11: Onzeald for Breast Cancer (February 27, 2020)
66 Table 12: Leronlimab for Breast Cancer (January 31, 2020)
67 Table 13: Oral Paclitaxel for Breast Cancer (December 13, 2019)
68 Table 14: Perjeta/Herceptin SQ FDC for Breast Cancer (December 12, 2019)
69 Table 15: Enhertu for Breast Cancer (December 11, 2019)
71 Table 16: Tukysa for Breast Cancer (December 11, 2019)
72 Table 17: MCLA-128 for Breast Cancer (October 23, 2019)
73 Table 18: Margetuximab for Breast Cancer (October 22, 2019)
74 Table 19: Tukysa for Breast Cancer (October 21, 2019)
76 Table 20: Verzenio for Breast Cancer (September 28, 2019)
77 Table 21: Oral Paclitaxel for Breast Cancer (August 7, 2019)
78 Table 22: Multiple Drugs for Breast Cancer (June 25, 2019)
79 Table 23: Margetuximab for Breast Cancer (June 4, 2019)
81 Table 24: Nerlynx for Breast Cancer (June 4, 2019)
83 Table 25: Perjeta for Breast Cancer (June 2, 2019)
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
Do you have a subscription to Datamonitor Healthcare, Biomedtracker or Meddevicetracker? You may already have access to these reports, contact your account manager or email pharma@informabi.com for further help or assistance.
Head and Neck Cancer Disease Coverage Forecast and Market Analysis to 2024 
Sign up to the