Disease Analysis: Triple-Negative Breast Cancer
Author: Millie Gray
Publisher: Datamonitor Healthcare
- Description
- Contents
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Latest key takeaways
- Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and does not involve the overexpression of human epidermal growth factor 2 (HER2). 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 TNBC market will experience rapid 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 will be the approval and subsequent uptake of new targeted therapies and immunotherapies. The market for TNBC is also becoming increasingly segmented by biomarker status, creating fierce competition among both approved and pipeline therapies for small patient populations.
- There will likely be reimbursement issues as payers may initially hesitate to reimburse new treatments based on novel biomarkers. Additionally, payers may be unwilling to reimburse expensive therapies with only incremental improvements in patient outcomes.
- Avastin’s relatively poor risk-to-benefit profile has led to its removal from the US market and difficulties with reimbursement in the UK, where it was also removed from the Cancer Drugs Fund. Additionally, Avastin faces biosimilar competition following its 2019 patent expiry.
- Abraxane is a preferred treatment regimen in cases of hypersensitivity to paclitaxel, and has demonstrated efficacy as a first- and second-line monotherapy treatment. The recent approval in combination with Tecentriq has boosted Abraxane’s clinical and commercial potential, although it is forecast to steadily lose market share after the introduction of generics in the EU in 2019 and in the US in 2022.
- Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1)-targeted monoclonal antibodies for TNBC are forecast to become the best-selling class of drugs for this indication. Tecentriq in combination with Abraxane was the first immunotherapy approved for TNBC patients in the first-line setting, but the failure of the confirmatory Phase III IMpassion131 study of the combination of Tecentriq and paclitaxel as a first-line treatment for TNBC patients with PD-L1-positive tumors has allowed recently approved competitor Keytruda to gain market share in the first-line setting. Following this, Genentech announced its decision to voluntarily withdraw the US accelerated approval for Tecentriq. Although Tecentriq is still approved in the five major European markets and Japan, this is still a significant blow for the drug’s commercial outlook and will allow competitor Keytruda to gain significant ground. However, Roche and Chugai have ongoing trials investigating Tecentriq in both the neoadjuvant and adjuvant settings which may allow Tecentriq to maintain some market share. Moreover, data from the ongoing IMpassion132 trial may allow Tecentriq to re-enter the first-line US TNBC market, but these data will likely not be released until the trial’s primary completion date in 2023, allowing Keytruda to gain dominance in this indication. Furthermore, after the release of event-free survival data from the Phase III KEYNOTE-522 trial, Keytruda has gained approval in the neoadjuvant/adjuvant setting first in the US, which will likely limit Tecentriq’s uptake.
- Although approved PARP inhibitors Lynparza and Talzenna are restricted to the relatively small germline BRCA1/2-mutated (gBRCAm) population, they are forecast to dominate within this patient segment. An expected label expansion into the adjuvant treatment setting for gBRCAm patients will add to Lynparza’s sales, making it one of the best-selling TNBC therapies over the next 10 years.
- Halaven became a standard of care for third-line and later treatment of TNBC following approval, but its market share has declined due to competition with recently approved and current pipeline drugs utilizing Halaven as a comparator therapy in clinical trials. Halaven is currently in development with the CXCR4 inhibitor balixafortide, and despite showing efficacy in a Phase Ib study, recent results from the Phase III FORTRESS study were resoundingly negative, likely meaning the end of balixafortide’s development in this indication and the continued decline of Halaven’s market share.
- In early 2020, Trodelvy received accelerated approval in the US for the treatment of TNBC patients who have failed at least two prior therapies, based on positive efficacy results in a Phase I/II study. Given the high unmet need and poor prognosis in this line of treatment, Trodelvy has experienced remarkably quick uptake after its launch despite the inclusion of two black box warnings on its label. The confirmatory Phase III ASCENT study was recently halted early due to evidence of strong efficacy, and the FDA granted full approval to Trodelvy in April 2021.
- Capivasertib and Piqray are both in development in the front-line setting for the 25–30% of patients who present with PTEN/PIK3CA/Akt-altered tumors. While these novel therapies will dominate within in this subgroup, their overall commercial potential is limited due to the biomarker restriction. Capivasertib will likely be the first Akt inhibitor to market after late-phase competitor ipatasertib failed in the Phase III IPATunity130 trial and Roche’s subsequent decision to discontinue the Phase III IPATunity170 trial.
- Key recent events include the release of updated results from the Phase III KEYNOTE-522 trial of Keytruda, as well as the FDA’s meeting re-examining Tecentriq’s accelerated approval in the first-line setting.
- Key upcoming catalysts for late 2021 and early 2022 include topline readouts from the Phase II VIOLETTE study of Lynparza and olaparib, and from the Phase II FACT 2 study of Nerlynx.
- 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
8 OVERVIEW
8 Latest key takeaways
10 DISEASE BACKGROUND
10 Definition
10 Risk factors
11 Symptoms
11 Diagnosis
11 Patient segmentation
12 Prognosis
14 TREATMENT
14 Referral patterns
14 Operable Stage I–III TNBC
14 Inoperable Stage III TNBC
14 Recommended neoadjuvant/adjuvant chemotherapy regimens
15 Treatment guidelines for Stage IV or recurrent TNBC
19 EPIDEMIOLOGY
22 Breast cancer subtypes
24 MARKETED DRUGS
30 PIPELINE DRUGS
46 KEY REGULATORY EVENTS
46 Keeping Track: Keytruda’s TNBC Label Grows
46 Roche Withdraws MAA For Tecentriq In Early Or Locally Advanced TNBC
46 Genentech’s Tecentriq Should Keep Its Accelerated Approval In Breast Cancer For Now, ODAC Says
46 Genentech’s Hopes For Keeping Tecentriq Breast Cancer Claim May Rest With Trial In Early Disease Recurrence
47 Gilead’s Trodelvy Gets Full Approval For TNBC
47 Gilead’s Trodelvy To Test UK Innovative Drug Pathway
47 Gilead Sciences/Immunomedics Seek EU Fast-Track For Sacituzumab Govitecan
48 Setback For Athenex, Hanmi As CRL Requests New Trial
48 Modeling Is Not a Drug Approval Pathway: Why Merck Flunked Keytruda’s TNBC Advisory Panel
48 Keytruda Takes On Tecentriq In TNBC Market
48 Centus Gets European Bevacizumab Approval
49 Samsung Bioepis Receives EU Bevacizumab Approval
50 PROBABILITY OF SUCCESS
51 LICENSING AND ASSET ACQUISITION DEALS
51 BMS, Eisai Team Up To Accelerate Development Of Solid-Tumor ADC
51 SELLAS Licenses Greater China Rights For Immunotherapies To 3D
51 Boehringer Buys Antibody-Drug Conjugates Biotech NBE For €1.18bn
51 Twice As Nice: Seattle Genetics, Merck & Co. Partner On Two Cancer Drugs
52 Gilead Buys Pipeline-In-A-Product With $21bn Immunomedics Deal
52 TriSalus Buys Dynavax’s Melanoma/Breast Cancer Therapy
53 CLINICAL TRIAL LANDSCAPE
55 Sponsors by status
55 Sponsors by phase
56 Recent events
59 DRUG ASSESSMENT MODEL
62 MARKET DYNAMICS
63 FUTURE TRENDS
63 Approvals and subsequent uptake of new targeted therapies and immunotherapies will drive growth in the TNBC market over the forecast period
63 Keytruda will overtake Tecentriq in the TNBC market during the forecast period
63 The PARP inhibitors will see significant use in the subset of TNBC patients with BRCA mutations over the forecast period
64 ADCs will dominate in the second-line and later setting over the forecast period
65 CONSENSUS FORECASTS
70 RECENT EVENTS AND ANALYST OPINION
70 Multiple Drugs for Breast Cancer (June 5, 2021)
70 Trodelvy for Breast Cancer (June 4, 2021)
71 Keytruda for Breast Cancer (May 13, 2021)
72 Tecentriq for Breast Cancer (April 27, 2021)
74 Tecentriq for Breast Cancer (April 23, 2021)
75 Keytruda for Breast Cancer (March 29, 2021)
76 Oral Paclitaxel for Breast Cancer (March 1, 2021)
77 Keytruda for Breast Cancer (February 9, 2021)
78 Keytruda for Breast Cancer (February 5, 2021)
79 Eganelisib for Breast Cancer (December 9, 2020)
81 Oral Paclitaxel for Breast Cancer (December 9, 2020)
82 Ipatasertib for Breast Cancer (September 30, 2020)
83 Tecentriq for Breast Cancer (September 19, 2020)
85 Tecentriq for Breast Cancer (September 19, 2020)
87 Trodelvy for Breast Cancer (September 19, 2020)
88 Tecentriq for Breast Cancer (August 6, 2020)
91 KEY UPCOMING EVENTS
93 KEY OPINION LEADER INSIGHTS
94 UNMET NEEDS
95 BIBLIOGRAPHY
97 APPENDIX
LIST OF FIGURES
12 Figure 1: Triple-negative breast cancer patient segmentation
15 Figure 2: Recommended neoadjuvant/adjuvant chemotherapy regimens
21 Figure 3: Trends in incident cases of breast cancer, 2018–27
30 Figure 4: Overview of pipeline drugs for breast cancer in the US
30 Figure 5: Pipeline drugs for breast cancer, by company
31 Figure 6: Pipeline drugs for breast cancer, by drug type
31 Figure 7: Pipeline drugs for breast cancer, by classification
50 Figure 8: Probability of success in the breast cancer pipeline
53 Figure 9: Clinical trials in breast cancer
53 Figure 10: Top 10 drugs for clinical trials in breast cancer
54 Figure 11: Top 10 companies for clinical trials in breast cancer
54 Figure 12: Trial locations in breast cancer
55 Figure 13: Breast cancer trials status
56 Figure 14: Breast cancer trials sponsors, by phase
59 Figure 15: Datamonitor Healthcare’s drug assessment summary for triple-negative breast cancer
62 Figure 16: Market dynamics in triple-negative breast cancer
63 Figure 17: Future trends in triple-negative breast cancer
81 Figure 18: Eganelisib for Breast Cancer (December 9, 2020): Phase II – MARIO-3
82 Figure 19: Oral Paclitaxel for Breast Cancer (December 9, 2020): Phase III – KX-ORAX-001 (S. America)
83 Figure 20: Ipatasertib for Breast Cancer (September 30, 2020): Phase III – IPATunity130
85 Figure 21: Tecentriq for Breast Cancer (September 19, 2020): Phase III – IMpassion 130 (w/Nab-Paclitaxel), Phase III – IMpassion131 (w/Paclitaxel, 1st-Line)
87 Figure 22: Tecentriq for Breast Cancer (September 19, 2020): Phase III – IMpassion031 (w/Nab-Paclitaxel)
88 Figure 23: Trodelvy for Breast Cancer (September 19, 2020): Phase III – ASCENT (TNBC)
90 Figure 24: Tecentriq for Breast Cancer (August 6, 2020): Phase III – IMpassion131 (w/Paclitaxel, 1st-Line)
91 Figure 25: Key upcoming events in breast cancer (one of two)
92 Figure 26: Key upcoming events in breast cancer (two of two)
94 Figure 27: Unmet needs in triple-negative breast cancer
LIST OF TABLES
17 Table 1: Preferred branded treatment regimens for patients with Stage IV or recurrent triple-negative breast cancer
20 Table 2: Incident cases of breast cancer, 2018–27
22 Table 3: Five-year prevalent cases of breast cancer, 2018–27
23 Table 4: Breast cancer subtypes
25 Table 5: Marketed drugs for triple-negative breast cancer
32 Table 6: Pipeline drugs for triple-negative breast cancer in the US
66 Table 7: Historical global sales, by drug ($m), 2016–20
68 Table 8: Forecasted global sales, by drug ($m), 2021–25
70 Table 9: Multiple Drugs for Breast Cancer (June 5, 2021)
71 Table 10: Trodelvy for Breast Cancer (June 4, 2021)
72 Table 11: Keytruda for Breast Cancer (May 13, 2021)
73 Table 12: Tecentriq for Breast Cancer (April 27, 2021)
74 Table 13: Tecentriq for Breast Cancer (April 23, 2021)
75 Table 14: Keytruda for Breast Cancer (March 29, 2021)
76 Table 15: Oral Paclitaxel for Breast Cancer (March 1, 2021)
77 Table 16: Keytruda for Breast Cancer (February 9, 2021)
78 Table 17: Keytruda for Breast Cancer (February 5, 2021)
80 Table 18: Eganelisib for Breast Cancer (December 9, 2020)
81 Table 19: Oral Paclitaxel for Breast Cancer (December 9, 2020)
82 Table 20: Ipatasertib for Breast Cancer (September 30, 2020)
84 Table 21: Tecentriq for Breast Cancer (September 19, 2020)
86 Table 22: Tecentriq for Breast Cancer (September 19, 2020)
87 Table 23: Trodelvy for Breast Cancer (September 19, 2020)
89 Table 24: Tecentriq for Breast Cancer (August 6, 2020)
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