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). The publisher 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.
- 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.
- 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. Although Tecentriq’s accelerated approval was in danger following the failure of the Phase III IMpassion131 trial, the FDA Oncologic Drugs Advisory Committee recently voted to maintain Tecentriq’s accelerated approval in the first-line setting pending data from the Phase III IMpassion132 trial. However, competitor Keytruda is expected to overtake Tecentriq in the first-line setting due to its wide variety of chemotherapy backbone options. After the Oncologic Drugs Advisory Committee unanimously voted to delay an approval decision pending more mature event-free survival data from the Phase III KEYNOTE-522 trial, Keytruda’s possible entry into the lucrative neoadjuvant/adjuvant market has been significantly delayed.
- 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 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 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 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. 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 FDA Oncologic Drugs Advisory Committee meeting for Keytruda’s supplemental Biologics License Application in the neoadjuvant/adjuvant setting, as well as the meeting re-examining Tecentriq’s accelerated approval in the first-line setting.
- Key upcoming catalysts for 2021 include topline read-outs from the Phase III FORTRESS study of balixafortide and Halaven and from the Phase III OlympiA study of Lynparza.
- The overall likelihood of approval of a Phase I breast cancer asset is 7.8%, 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.
Table of Contents
OVERVIEW
DISEASE BACKGROUND
TREATMENT
EPIDEMIOLOGY
KEY REGULATORY EVENTS
LICENSING AND ASSET ACQUISITION DEALS
CLINICAL TRIAL LANDSCAPE
FUTURE TRENDS
RECENT EVENTS AND ANALYST OPINION
LIST OF FIGURES
LIST OF TABLES
