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, although the label was restricted to patients with PD-L1-positive tumors. Roche and Chugai are pursuing label expansions for Tecentriq in both the neoadjuvant and adjuvant settings. Keytruda is expected to be approved regardless of biomarker status in the lucrative neoadjuvant/adjuvant market and is also forecast to compete with Tecentriq in the first-line 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 highest-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 will face biosimilar competition from 2019 onward.
- 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.
- Trodelvy recently 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 will experience fast uptake once launched 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 plans to file for a full approval in the fourth quarter of 2020.
- The target population for the pipeline protein kinase B alpha (Akt) inhibitors ipatasertib and capivasertib will likely be limited to patients who present with phosphatase and tensin homolog (PTEN)/phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)/AKT-altered tumors. Both are in development in combination with paclitaxel, and the anticipated competition between these drugs may make it difficult for one to dominate in this segment.
- Key recent events include the US accelerated approval of Trodelvy, as well as a number of Phase III trial topline results, including Tecentriq’s Phase III success as a neoadjuvant therapy in IMpassion031 and its failure in the Phase III IMpassion131 study.
- Key upcoming catalysts for 2020 and early 2021 include the expected approvals of Keytruda as both a neoadjuvant and first-line therapy, as well as top-line results from the Phase III IPATunity130 study of ipatasertib and paclitaxel, and the Phase III FORTRESS study of POL6326 and Halaven.
- 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 9.4 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
27 PIPELINE DRUGS
43 KEY REGULATORY EVENTS
43 India’s SPARC Keeps Paclitaxel Ambition Burning For Now
43 Mid-2020 Will Be Decisive For Immunomedics’ Sacituzumab Govitecan
43 England’s NICE Rejects Tecentriq In Triple-Negative Breast Cancer
43 Tecentriq Takes EU Lead In Triple-Negative Breast Cancer
44 Roche Wins Two French Early Access Programs In Breast Cancer
45 PROBABILITY OF SUCCESS
46 LICENSING AND ASSET ACQUISITION DEALS
46 Taiho Acquires Asian Rights To Arcus IO Candidate
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 Approvals and subsequent uptake for new targeted therapies and immunotherapies will drive growth in the TNBC market over the forecast period
55 PD-1/PD-L1 inhibitors will be the top-selling class for TNBC during the forecast period
55 PARP inhibitors will see significant use in the TNBC market over the forecast period
56 ADCs will have a moderate share of the TNBC market over the forecast period
57 CONSENSUS FORECASTS
59 RECENT EVENTS AND ANALYST OPINION
59 Trodelvy for Breast Cancer (April 6, 2020)
60 Onzeald for Breast Cancer (February 27, 2020)
61 Keytruda for Breast Cancer (February 12, 2020)
62 Leronlimab for Breast Cancer (January 31, 2020)
63 Pegilodecakin for Breast Cancer (January 30, 2020)
63 Oraxol for Breast Cancer (December 13, 2019)
64 Imprime PGG for Breast Cancer (December 11, 2019)
66 Keytruda for Breast Cancer (September 29, 2019)
68 Trilaciclib for Breast Cancer (September 28, 2019)
69 Keytruda for Breast Cancer (September 28, 2019)
71 Oraxol for Breast Cancer (August 7, 2019)
73 ZEN-3694 for Breast Cancer (August 6, 2019)
74 Keytruda for Breast Cancer (July 29, 2019)
75 Mavorixafor for Breast Cancer (July 17, 2019)
76 MGA012 for Breast Cancer (July 2, 2019)
77 Multiple Drugs for Breast Cancer (June 25, 2019)
78 Trilaciclib for Breast Cancer (June 18, 2019)
80 Talzenna for Breast Cancer (June 3, 2019)
81 TAVO for Breast Cancer (May 22, 2019)
82 Keytruda for Breast Cancer (May 20, 2019)
84 Trodelvy for Breast Cancer (April 29, 2019)
86 KEY UPCOMING EVENTS
87 KEY OPINION LEADER INSIGHTS
88 UNMET NEEDS
89 BIBLIOGRAPHY
90 Prescription information
91 APPENDIX
LIST OF FIGURES
12 Figure 1: TNBC patient segmentation
15 Figure 2: Recommended neoadjuvant/adjuvant chemotherapy regimens
19 Figure 3: Trends in incident cases of breast cancer, 2018–27
27 Figure 4: Overview of pipeline drugs for breast cancer in the US
27 Figure 5: Pipeline drugs for breast cancer, by company
28 Figure 6: Pipeline drugs for breast cancer, by drug type
28 Figure 7: Pipeline drugs for breast cancer, by classification
45 Figure 8: Probability of success in the breast cancer pipeline
47 Figure 9: Clinical trials in breast cancer
47 Figure 10: Top 10 drugs for clinical trials in breast cancer
48 Figure 11: Top 10 companies for clinical trials in breast cancer
48 Figure 12: Trial locations in breast cancer
49 Figure 13: Breast cancer trials status
50 Figure 14: Breast cancer trials sponsors, by phase
52 Figure 15: Datamonitor Healthcare’s drug assessment summary for triple-negative breast cancer
54 Figure 16: Market dynamics in triple-negative breast cancer
55 Figure 17: Future trends in triple-negative breast cancer
62 Figure 18: Keytruda for Breast Cancer (February 12, 2020): Phase III – KEYNOTE-355 (TNBC)
66 Figure 19: Imprime PGG for Breast Cancer (December 11, 2019): Phase II – w/Pembrolizumab (TNBC)
68 Figure 20: Keytruda for Breast Cancer (September 29, 2019): Phase III – KEYNOTE-522 (TNBC)
69 Figure 21: Trilaciclib for Breast Cancer (September 28, 2019): Phase II – mTNBC
71 Figure 22: Keytruda for Breast Cancer (September 28, 2019): Phase III – KEYNOTE-119 (mTNBC)
73 Figure 23: Oraxol for Breast Cancer (August 7, 2019): Phase III – KX-ORAX-001 (S. America)
75 Figure 24: Keytruda for Breast Cancer (July 29, 2019): Phase III – KEYNOTE-522 (TNBC)
80 Figure 25: Trilaciclib for Breast Cancer (June 18, 2019): Phase II – mTNBC
82 Figure 26: TAVO for Breast Cancer (May 22, 2019): Phase II – KEYNOTE-890 (w/Keytruda; mTNBC)
84 Figure 27: Keytruda for Breast Cancer (May 20, 2019): Phase III – KEYNOTE-119 (mTNBC)
86 Figure 28: Key upcoming events in breast cancer
88 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 TNBC
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
29 Table 6: Pipeline drugs for triple-negative breast cancer in the US
57 Table 7: Historical global sales, by drug ($m), 2015-19
58 Table 8: Forecasted global sales, by drug ($m), 2020–24
59 Table 9: Trodelvy for Breast Cancer (April 6, 2020)
60 Table 10: Onzeald for Breast Cancer (February 27, 2020)
61 Table 11: Keytruda for Breast Cancer (February 12, 2020)
62 Table 12: Leronlimab for Breast Cancer (January 31, 2020)
63 Table 13: Pegilodecakin for Breast Cancer (January 30, 2020)
64 Table 14: Oraxol for Breast Cancer (December 13, 2019)
65 Table 15: Imprime PGG for Breast Cancer (December 11, 2019)
67 Table 16: Keytruda for Breast Cancer (September 29, 2019)
68 Table 17: Trilaciclib for Breast Cancer (September 28, 2019)
70 Table 18: Keytruda for Breast Cancer (September 28, 2019)
72 Table 19: Oraxol for Breast Cancer (August 7, 2019)
73 Table 20: ZEN-3694 for Breast Cancer (August 6, 2019)
74 Table 21: Keytruda for Breast Cancer (July 29, 2019)
76 Table 22: Mavorixafor for Breast Cancer (July 17, 2019)
77 Table 23: MGA012 for Breast Cancer (July 2, 2019)
78 Table 24: Multiple Drugs for Breast Cancer (June 25, 2019)
79 Table 25: Trilaciclib for Breast Cancer (June 18, 2019)
80 Table 26: Talzenna for Breast Cancer (June 3, 2019)
81 Table 27: TAVO for Breast Cancer (May 22, 2019)
83 Table 28: Keytruda for Breast Cancer (May 20, 2019)
84 Table 29: Trodelvy for Breast Cancer (April 29, 2019)
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