Disease Analysis: HR+/HER2- Breast Cancer
Author: Zachary McLellan
Publisher: Datamonitor Healthcare
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Overview
Hormone receptor-positive (HR+) is the most common breast cancer subtype, with approximately 70% of breast cancers presenting with overexpression of estrogen receptors, progesterone receptors, or both. Overexpression of the hormone receptors allows estrogen and progesterone to drive tumor growth and proliferation. Therefore, endocrine therapy remains the standard treatment for advanced patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
Latest key takeaways
- 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 prevalent cases of breast cancer are expected to increase to 2.3 million and 9.3 million cases, respectively.
- CDK4/6 inhibitors remain the standard treatment for advanced and metastatic HR+/HER2- patients. Datamonitor Healthcare expects their uptake to increase significantly over the forecast period as Verzenio and Kisqali are projected to receive strategic label expansions into the adjuvant treatment setting for early-stage HR+/HER2- breast cancer patients. Verzenio is set to be the first of these therapies approved in early breast cancer, with US and EU regulatory decisions expected towards the end of 2021. Submissions were based on positive results from the Phase III monarchE trial. Ibrance is not forecasted to receive a similar approval after the failure of the PALLAS and PENELOPE-B trials.
- The PARP inhibitors have become the standard option for gBRCAm+ breast cancer patients. Despite their efficacy in this population, their overall commercial potential will remain limited in the near term by their positioning in this niche segment. Expansion into the adjuvant setting for earlier-stage disease will improve their outlook, beginning with Lynparza, which improved the risk of invasive breast cancer recurrence, second cancer, or death by 42% over placebo in the Phase III OlympiA trial.
- Fulvestrant remains a key therapy across patient segments. Guideline recommendations for use at first line and subsequent lines of therapy, an indication for use in combination with the CDK4/6 inhibitors, as well as expansion as part of a combination with Piqray highlight its broad utility. However, generic competition will continue to erode branded Faslodex’s market share.
- Piqray is the first PI3K inhibitor approved for use in breast cancer. The overall potential of Piqray will be somewhat limited by its side-effect profile that includes high rates of neutropenia, nausea, hyperglycemia, and diarrhea. It also faces potential intra-class competition from late-phase PI3K/Akt/mTOR pathway inhibitors ipatasertib, capivasertib, and inavolisib.
- Afinitor remains a standard option for patients who progress on prior endocrine therapy, and is typically used post-CDK4/6 inhibitor treatment. However, generic versions of the drug will continue to take market share over the forecast period.
- Generic and biosimilar versions of key branded therapies will slow growth of the HR+/HER2- breast cancer market. The largest impact will come from palbociclib generics, although their launch is now delayed until at least 2027 following the extension of Ibrance’s key ‘739 patent.
- Development of pan-Akt inhibitor ipatasertib was suspended following poor results from the Phase III IPATunity130 trial testing the drug in combination with paclitaxel for the first-line treatment of advanced or metastatic PIK3CA/AKT1/PTEN-altered patients. In the study, ipatasertib failed to improve PFS over placebo in both the HR+/HER2- and triple-negative cohorts. The Phase Ib/III IPATunity150 trial testing ipatasertib in combination with Ibrance and fulvestrant in relapsed HR+ patients is ongoing, but Roche has removed ipatasertib from its breast cancer pipeline and it is not forecast to reach the breast cancer market.
- Several oral SERDs are in late-phase development, being tested against standard hormone therapy across a number of segments. Data are needed from late-phase trials, but improved or comparable outcomes along with oral administration will provide an advantage in select patient populations. Oral SERDs in late-phase development include Roche’s giredestrant, Sanofi’s SAR439859, and AstraZeneca’s AZD9833.
- Checkpoint inhibitors are now being trialed in the early-stage segment of HR+/HER2- breast cancer. The PD-1 inhibitors Keytruda and Opdivo are being studied as periadjuvant therapies for high-risk, early-stage HR+/HER2- breast cancer patients in the Phase III KEYNOTE-756 and CheckMate 7FL studies, respectively. Data are lacking from these trials, and it is likely that regulatory agencies will wait for event-free survival or even OS outcomes before considering a regulatory submission. As such, their potential approvals are likely to occur in the late 2020s.
- Key upcoming events include the final OS analysis for eftilagimod alpha in the Phase IIb AIPAC trial, topline results for Trodelvy in the Phase III TROPICS-02 study, first results from elacestrant in the Phase III EMERALD study, as well as a CHMP opinion and EU and US supplementary approval decisions for Verzenio in high-risk, early-stage HR+/HER2- breast cancer patients.
- A relatively high proportion of trials for breast cancer have been in Phase II (44.8%), compared to other indications. The US, Spain, and France have seen the greatest number of breast cancer trials globally. Within Asia, China has the top spot. Clinical trial activity in the breast cancer space is dominated by completed trials. Roche has the highest number of completed clinical trials for breast cancer, with 472 trials.
- The overall likelihood of approval of a Phase I breast cancer asset is 7.9%, and the average probability a drug advances from Phase III is 56.1%. Breast cancer drugs, on average, take 9.7 years from Phase I to approval, compared to 9.6 years in the overall oncology space.
CONTENTS
7 OVERVIEW
7 Latest key takeaways
9 DISEASE BACKGROUND
9 Definition
9 Risk factors
10 Symptoms
11 Diagnosis
11 Patient segmentation
12 Prognosis
13 TREATMENT
13 Referral patterns
13 Operable Stage I–III HR+/HER2- breast cancer
13 Inoperable Stage III HR+/HER2- breast cancer
14 Treatment guidelines for Stage IV or recurrent HR+/HER2- breast cancer
17 EPIDEMIOLOGY
17 Incidence and prevalence methodology
20 Breast cancer subtypes
22 MARKETED DRUGS
29 PIPELINE DRUGS
48 KEY REGULATORY EVENTS
48 Piqray: German Withdrawal, European Reimbursement Deals & Broader Indication Plans
48 Setback For Athenex, Hanmi As CRL Requests New Trial
48 New Evidence For Kisqali Secures Funding In England For Second-Line Use
49 Lilly Undeterred By UK NICE Funding Blow For Second-Line Use Of Verzenios
49 Generic Ibrance Among Latest China Approvals
49 EU Decision Thwarts Novartis’s Near-Term Piqray Ambitions
50 EU Indication Restricted For Novartis’s Newly Approved Piqray
51 PROBABILITY OF SUCCESS
52 LICENSING AND ASSET ACQUISITION DEALS
52 Arvinas, Pfizer Partner To Pursue Best-In-Class Breast Cancer Strategy
52 Innovent Buys Into Ascentage, Opening New China Biopharma Chapter
52 Celcuity Licenses Breast Cancer Clinical Candidate From Pfizer
53 SELLAS Licenses Greater China Rights For Immunotherapies To 3D
53 Merck Pays $2.75bn To Access VelosBio’s ROR1-Targeting ADCs
53 Bayer Licenses ER+ Breast Cancer Candidate From Systems Biology
54 Twice As Nice: Seattle Genetics, Merck & Co. Partner On Two Cancer Drugs
54 TriSalus Buys Dynavax’s Melanoma/Breast Cancer Therapy
55 CLINICAL TRIAL LANDSCAPE
57 Sponsors by status
57 Sponsors by phase
58 Recent events
63 DRUG ASSESSMENT MODEL
67 MARKET DYNAMICS
68 FUTURE TRENDS
68 CDK4/6 inhibitors will remain the best-selling class for HR+/HER2- breast cancer
68 Several oral SERDs are in late-phase development
68 Treatment options in advanced patients will be increasingly segmented
69 Generic and biosimilar uptake will slow, but not reverse, growth
70 CONSENSUS FORECASTS
75 RECENT EVENTS AND ANALYST OPINION
75 POL6326 for Breast Cancer (June 28, 2021)
76 Lynparza for Breast Cancer (June 3, 2021)
78 Giredestrant for Breast Cancer (May 19, 2021)
80 H3B-6545 for Breast Cancer (May 19, 2021)
81 Rintodestrant for Breast Cancer (May 19, 2021)
82 SAR439859 for Breast Cancer (May 19, 2021)
83 Oral Paclitaxel for Breast Cancer (March 1, 2021)
85 ARV-471 for Breast Cancer (December 14, 2020)
86 Tesetaxel for Breast Cancer (December 11, 2020)
87 Oral Paclitaxel for Breast Cancer (December 9, 2020)
88 Ibrance for Breast Cancer (October 9, 2020)
89 Ibrance for Breast Cancer (September 20, 2020)
90 Verzenio for Breast Cancer (September 20, 2020)
92 Ipatasertib for Breast Cancer (September 18, 2020)
94 Tesetaxel for Breast Cancer (August 24, 2020)
97 KEY UPCOMING EVENTS
99 KEY OPINION LEADER INSIGHTS
100 BIBLIOGRAPHY
102 APPENDIX
LIST OF FIGURES
12 Figure 1: TNM staging system for breast cancer
14 Figure 2: Recommended adjuvant endocrine therapy regimens for HR+/HER2- breast cancer
19 Figure 3: Trends in incident cases of breast cancer, 2018–27
29 Figure 4: Overview of pipeline drugs for breast cancer in the US
29 Figure 5: Pipeline drugs for breast cancer, by company
30 Figure 6: Pipeline drugs for breast cancer, by drug type
30 Figure 7: Pipeline drugs for breast cancer, by classification
51 Figure 8: Probability of success in the breast cancer pipeline
55 Figure 9: Clinical trials in breast cancer
55 Figure 10: Top 10 drugs for clinical trials in breast cancer
56 Figure 11: Top 10 companies for clinical trials in breast cancer
56 Figure 12: Trial locations in breast cancer
57 Figure 13: Breast cancer trials status
58 Figure 14: Breast cancer trials sponsors, by phase
63 Figure 15: Datamonitor Healthcare’s drug assessment summary for HR+/HER2- breast cancer
67 Figure 16: Market dynamics in HR+/HER2- breast cancer
68 Figure 17: Future trends in HR+/HER2- breast cancer
76 Figure 18: POL6326 for Breast Cancer (June 28, 2021): Phase III – FORTRESS
78 Figure 19: Lynparza for Breast Cancer (June 3, 2021): Phase III – OlympiA (gBRCA, Adjuvant)
80 Figure 20: Giredestrant for Breast Cancer (May 19, 2021): Phase Ia/Ib – w/Palbociclib and/or LHRH Agonist
81 Figure 21: H3B-6545 for Breast Cancer (May 19, 2021): Phase I/II – Monotherapy (HER2 Negative Subjects)
87 Figure 22: Tesetaxel for Breast Cancer (December 11, 2020): Phase III – CONTESSA (HER2-/HR+/Prev. Taxane)
88 Figure 23: Oral Paclitaxel for Breast Cancer (December 9, 2020): Phase III – KX-ORAX-001 (S. America)
92 Figure 24: Verzenio for Breast Cancer (September 20, 2020): Phase III – monarchE
94 Figure 25: Ipatasertib for Breast Cancer (September 18, 2020): Phase III – IPATunity130
96 Figure 26: Tesetaxel for Breast Cancer (August 24, 2020): Phase III – CONTESSA (HER2-/HR+/Prev. Taxane)
97 Figure 27: Key upcoming events in breast cancer
98 Figure 28: Key upcoming events in breast cancer (continued)
LIST OF TABLES
15 Table 1: Branded treatment regimens for patients with Stage IV or recurrent HR+/HER2- breast cancer
18 Table 2: Incident cases of breast cancer, 2018–27
20 Table 3: Five-year prevalent cases of breast cancer, 2018–27
21 Table 4: Breast cancer subtypes
23 Table 5: Marketed drugs for HR+/HER2- breast cancer
31 Table 6: Pipeline drugs for HR+/HER2- breast cancer in the US
71 Table 7: Historical global sales, by drug ($m), 2016–20
73 Table 8: Forecasted global sales, by drug ($m), 2021–25
75 Table 9: POL6326 for Breast Cancer (June 28, 2021)
76 Table 10: Lynparza for Breast Cancer (June 3, 2021)
79 Table 11: Giredestrant for Breast Cancer (May 19, 2021)
80 Table 12: H3B-6545 for Breast Cancer (May 19, 2021)
82 Table 13: Rintodestrant for Breast Cancer (May 19, 2021)
83 Table 14: SAR439859 for Breast Cancer (May 19, 2021)
84 Table 15: Oral Paclitaxel for Breast Cancer (March 1, 2021)
85 Table 16: ARV-471 for Breast Cancer (December 14, 2020)
86 Table 17: Tesetaxel for Breast Cancer (December 11, 2020)
87 Table 18: Oral Paclitaxel for Breast Cancer (December 9, 2020)
89 Table 19: Ibrance for Breast Cancer (October 9, 2020)
90 Table 20: Ibrance for Breast Cancer (September 20, 2020)
91 Table 21: Verzenio for Breast Cancer (September 20, 2020)
93 Table 22: Ipatasertib for Breast Cancer (September 18, 2020)
95 Table 23: Tesetaxel for Breast Cancer (August 24, 2020)
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