Disease Analysis: Triple-Negative Breast Cancer
Author: Tara Hansen
Publisher: Datamonitor Healthcare
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Disease Overview
TNBC is a relatively rare breast cancer subtype. It is characterized by the absence of estrogen and progesterone receptors, and does not involve the overexpression of HER2. TNBC is associated with poor prognosis, a high risk of local recurrence, and poor disease-free and cancer-specific survival. It accounts for roughly 14% of breast cancers.
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 are 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.
- Programmed death-1 (PD-1)/programmed death-ligand 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, and Roche and Chugai are pursuing label expansions for Tecentriq in both the neoadjuvant and adjuvant settings. However, competitor Keytruda is expected to overtake Tecentriq in the first-line setting due to its wide variety of chemotherapy backbone options. Pending a positive vote from the FDA Oncologic Drugs Advisory Committee meeting on 9 February 2021, Keytruda is also expected be approved regardless of biomarker status in the lucrative neoadjuvant/adjuvant market.
- 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.
- Avastin’s relatively poor risk-to-benefit profile has led to 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.
- Halaven has become a standard of care for third-line and later treatment of TNBC since its approval, despite encountering challenges with reimbursement. Additionally, Halaven’s market share may increase with a potential label for use with the chemokine (C-X-C motif) receptor 4 (CXCR4) inhibitor balixafortide. The combination has received Fast Track status after showing promising early efficacy results in a Phase Ib study. The commercial potential of this combination will help to offset the decline in Halaven’s revenues caused by competition from a number of recently approved and current pipeline drugs.
- 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 Immunomedics filed for a full approval in December 2020.
- Capivasertib, ipatasertib, and Piqray are all in development in the front-line setting for the 25–30% of patients who present with phosphatase and tensin homolog (PTEN)/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)/protein kinase B alpha (Akt)-altered tumors. While these novel therapies will dominate within patients in this subgroup, their overall commercial potential is limited due to the biomarker restriction. After the failure of the Phase III IPATunity170 trial of ipatasertib, capivasertib will likely be the first Akt inhibitor to market.
- Key recent events include the US accelerated approval of Keytruda in the first-line setting, as well as the Phase III failure of ipatasertib in the TNBC cohort of IPATunity130.
- Key upcoming catalysts for 2021 include the FDA Oncologic Drugs Advisory Committee meeting for Keytruda’s supplemental Biologics License Application in the neoadjuvant/adjuvant setting, as well as topline results from the Phase III FORTRESS study of POL6326 and Halaven.
- The overall likelihood of approval of a Phase I breast cancer asset is 8.1%, and the average probability a drug advances from Phase III is 57.1%. 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
17 EPIDEMIOLOGY
20 Breast cancer subtypes
22 MARKETED DRUGS
28 PIPELINE DRUGS
44 KEY REGULATORY EVENTS
44 Keytruda Takes On Tecentriq In TNBC Market
44 Centus Gets European Bevacizumab Approval
44 Samsung Bioepis Receives EU Bevacizumab Approval
44 Updated: Multiple Biosimilars To Avastin Have Launched In EU
45 Samsung Bioepis Bevacizumab Nod Sets Stage For EU Throwdown
45 Triple-Negative Breast Cancer First In England As NICE Reverses Tecentriq Rejection
45 Immunomedics’ Trodelvy Will Be First ADC For Triple-Negative Breast Cancer
45 India’s SPARC Keeps Paclitaxel Ambition Burning For Now
47 PROBABILITY OF SUCCESS
48 LICENSING AND ASSET ACQUISITION DEALS
48 Twice As Nice: Seattle Genetics, Merck & Co. Partner On Two Cancer Drugs
48 Gilead Buys Pipeline-In-A-Product With $21bn Immunomedics Deal
48 TriSalus Buys Dynavax’s Melanoma/Breast Cancer Therapy
48 AZ Bets Big On ADCs As It Inks Second, $6bn Deal With Daiichi
49 Daiichi Sankyo Partners With Syneos Health For Development Of Enhertu And Other Cancer Drugs
49 Taiho Acquires Asian Rights To Arcus IO Candidate
50 CLINICAL TRIAL LANDSCAPE
51 Sponsors by status
52 Sponsors by phase
53 Recent events
56 DRUG ASSESSMENT MODEL
59 MARKET DYNAMICS
60 FUTURE TRENDS
60 Approvals and subsequent uptake for new targeted therapies and immunotherapies will drive growth in the TNBC market
over the forecast period
60 Keytruda will overtake Tecentriq in the TNBC market during the forecast period
60 The PARP inhibitors will see significant use in the subset of TNBC patients with BRCA mutations over the forecast period
61 ADCs will dominate in the second-line and later setting over the forecast period
62 CONSENSUS FORECASTS
64 RECENT EVENTS AND ANALYST OPINION
64 Eganelisib for Breast Cancer (December 9, 2020)
65 Oral Paclitaxel for Breast Cancer (December 9, 2020)
66 Ipatasertib for Breast Cancer (September 30, 2020)
68 Tecentriq for Breast Cancer (September 19, 2020)
70 Tecentriq for Breast Cancer (September 19, 2020)
72 Trodelvy for Breast Cancer (September 19, 2020)
73 Tecentriq for Breast Cancer (August 6, 2020)
75 Trodelvy for Breast Cancer (July 6, 2020)
76 Tecentriq for Breast Cancer (June 18, 2020)
77 Keytruda for Breast Cancer (May 13, 2020)
79 Trodelvy for Breast Cancer (April 6, 2020)
80 Onzeald for Breast Cancer (February 27, 2020)
81 Keytruda for Breast Cancer (February 12, 2020)
82 Vyrologix for Breast Cancer (January 31, 2020)
83 Pegilodecakin for Breast Cancer (January 30, 2020)
85 KEY UPCOMING EVENTS
86 KEY OPINION LEADER INSIGHTS
87 UNMET NEEDS
88 BIBLIOGRAPHY
89 Prescription information
91 APPENDIX
LIST OF FIGURES
12 Figure 1: Triple-negative breast cancer patient segmentation
15 Figure 2: Recommended neoadjuvant/adjuvant chemotherapy regimens
19 Figure 3: Trends in incident cases of breast cancer, 2018–27
28 Figure 4: Overview of pipeline drugs for breast cancer in the US
28 Figure 5: Pipeline drugs for breast cancer, by company
29 Figure 6: Pipeline drugs for breast cancer, by drug type
29 Figure 7: Pipeline drugs for breast cancer, by classification
47 Figure 8: Probability of success in the breast cancer pipeline
50 Figure 9: Clinical trials in breast cancer
50 Figure 10: Top 10 drugs for clinical trials in breast cancer
51 Figure 11: Top 10 companies for clinical trials in breast cancer
51 Figure 12: Trial locations in breast cancer
52 Figure 13: Breast cancer trials status
53 Figure 14: Breast cancer trials sponsors, by phase
56 Figure 15: Datamonitor Healthcare’s drug assessment summary for triple-negative breast cancer
59 Figure 16: Market dynamics in triple-negative breast cancer
60 Figure 17: Future trends in triple-negative breast cancer
65 Figure 18: Eganelisib for Breast Cancer (December 9, 2020): Phase II – MARIO-3
66 Figure 19: Oral Paclitaxel for Breast Cancer (December 9, 2020): Phase III – KX-ORAX-001 (S. America)
68 Figure 20: Ipatasertib for Breast Cancer (September 30, 2020): Phase III – IPATunity130
70 Figure 21: Tecentriq for Breast Cancer (September 19, 2020): Phase III – IMpassion 130 (w/Nab-Paclitaxel), Phase III -IMpassion131 (w/Paclitaxel, 1st-Line)
72 Figure 22: Tecentriq for Breast Cancer (September 19, 2020): Phase III – IMpassion031 (w/Nab-Paclitaxel)
73 Figure 23: Trodelvy for Breast Cancer (September 19, 2020): Phase III – ASCENT (TNBC)
75 Figure 24: Tecentriq for Breast Cancer (August 6, 2020): Phase III – IMpassion131 (w/Paclitaxel, 1st-Line)
76 Figure 25: Trodelvy for Breast Cancer (July 6, 2020): Phase III – ASCENT (TNBC)
79 Figure 26: Keytruda for Breast Cancer (May 13, 2020): Phase III – KEYNOTE-355 (TNBC)
82 Figure 27: Keytruda for Breast Cancer (February 12, 2020): Phase III – KEYNOTE-355 (TNBC)
85 Figure 28: Key upcoming events in breast cancer
87 Figure 29: Unmet needs in triple-negative breast cancer
LIST OF TABLES
16 Table 1: Preferred branded treatment regimens for patients with Stage IV or recurrent triple-negative 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 triple-negative breast cancer
30 Table 6: Pipeline drugs for triple-negative breast cancer in the US
62 Table 7: Historical global sales, by drug ($m), 2015–19
63 Table 8: Forecasted global sales, by drug ($m), 2020–24
64 Table 9: Eganelisib for Breast Cancer (December 9, 2020)
65 Table 10: Oral Paclitaxel for Breast Cancer (December 9, 2020)
67 Table 11: Ipatasertib for Breast Cancer (September 30, 2020)
68 Table 12: Tecentriq for Breast Cancer (September 19, 2020)
71 Table 13: Tecentriq for Breast Cancer (September 19, 2020)
72 Table 14: Trodelvy for Breast Cancer (September 19, 2020)
74 Table 15: Tecentriq for Breast Cancer (August 6, 2020)
75 Table 16: Trodelvy for Breast Cancer (July 6, 2020)
77 Table 17: Tecentriq for Breast Cancer (June 18, 2020)
78 Table 18: Keytruda for Breast Cancer (May 13, 2020)
79 Table 19: Trodelvy for Breast Cancer (April 6, 2020)
80 Table 20: Onzeald for Breast Cancer (February 27, 2020)
81 Table 21: Keytruda for Breast Cancer (February 12, 2020)
83 Table 22: Vyrologix for Breast Cancer (January 31, 2020)
84 Table 23: Pegilodecakin for Breast Cancer (January 30, 2020)
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