Meeting
2023 ASCO Annual Meeting
Reliance of agency-approved and guideline-recommended therapies on surrogate endpoints in triple-negative breast cancer (TNBC).
Authors
Kinisha Gala
The Larvol Group, LLC, San Francisco, CA
Kinisha Gala , Ankit Kalucha , Judith Pérez-Granado , Maria Garcia Requesens , Laura Vidal , Bruno Larvol , Mark Gramling , Kamal S. Saini
Organizations
The Larvol Group, LLC, San Francisco, CA, LabCorp Drug Development, Princeton, NJ, Labcorp Drug Development, Burlington, NC, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
Research Funding
No funding received
None.
Background: Surrogate endpoints, such as progression-free survival (PFS) and event-free survival (EFS), are used for accelerated approval in various cancers, including TNBC. Here we review the use of surrogates and clinical outcomes in determining agency approval and guideline recommendation. Methods: Phase 2/3 TNBC trials and trials including TNBC subgroups reporting hazard ratios (HR) for clinical and surrogate endpoints were identified through a systematic search of LARVOL CLIN, PubMed, and conference proceedings. Trials that only evaluated cytotoxic agents and did not report EFS, PFS and/ or overall survival (OS) HR values were excluded. We performed a descriptive analysis of agency and guideline approvals in relation to therapeutic benefit as measured by surrogate outcomes and OS. Results: 21 TNBC cohorts and 1 pooled analysis studying 17 different targeted therapies for TNBC were included. There are 3 targeted therapies that have agency approval and 7 targeted therapies that are recommended by either the NCCN, EMA and ASCO guidelines. Of the two FDA and EMA-approved therapies, pembrolizumab + chemotherapy (PBL + CHT) showed PFS/EFS benefit for early TNBC and PDL1+ metastatic (m) TNBC but only OS benefit for PDL1+ mTNBC, whereas sacituzumab showed significant benefit for both PFS and OS for mTNBC. Four therapies (olaparib for BRCA+ mTNBC, bevacizumab for early TNBC, talazoparib for BRCA+ mTNBC and PBL + CHT for PD-L1+ mTNBC) are recommended by guidelines without having a significant OS benefit. Conclusions: Surrogate outcomes are heavily relied upon for TNBC guideline recommendation. Despite the need for timely access to novel TNBC therapeutics, clinical outcomes should be followed to ensure benefit once they have been reached. An up-to-date digitized trial results repository would ensure expedient review of clinical endpoints.
| Clinical and Surrogate HR values for Approved and Guideline Recommended Drugs. | ||||||
|---|---|---|---|---|---|---|
| Trial | N | Intervention Arm Drugs | PFS HR (CI), p-value | OS HR (CI), p-value | Approvals | Guidelines |
| KEYNOTE-522 | 1174 | PBL + CHT | 0.63(0.48-0.82),0.001** | 0.72 (0.51-1.02) | FDA, EMA | ASCO |
| KEYNOTE-355 For PD-L1+(CPS ≥10) | 323 | PBL + CHT | 0.65 (0.49-0.86), 0.0012 | 0.73(0.55-0.95), 0.0093 | FDA, EMA | ASCO, ESMO, NCCN |
| ASCENT | 529 | Sacituzumab + CHT | 0.43 (0.35-0.54), 0.001 | 0.51 (0.41-0.62), 0.0001 | FDA, EMA | ASCO, ESMO |
| IMpassion1301 For PD-L1+ ≥ 1% | 369 | Atezolizumab + Nab-Paclitaxel | 0.60 (0.48-0.77), 0.0001 | 0.67(0.53-0.86) | EMA | ASCO, ESMO, NCCN |
| Olympiad* | 150 | Olaparib | 0.43 (0.29–0.63) | 0.93(0.62-1.43) | - | ASCO, ESMO, NCCN |
| EMBRACA* | 190 | Talazoparib | 0.60 (0.41–0.87) | 0.899 (0.634-1.276) | - | ASCO, ESMO |
| Pooled E2100, AVADO RIBBON-1* | 621 | Bevacizumab + CHT | 0.63 (0.52–0.76) | 0.96 (0.79-1.16) | - | ESMO |
Bold indicates statistical significance based on p-value or CI. Underline indicates the primary endpoint. 1FDA accelerated approval withdrawn in Aug 2021. *Only TNBC subgroup data shown. **EFS
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Abstract Details
Session Type
Publication Only
Session Title
Publication Only: Breast Cancer—Metastatic
Track
Breast Cancer
Sub Track
Triple-Negative
Citation
J Clin Oncol 41, 2023 (suppl 16; abstr e13085)
DOI
10.1200/JCO.2023.41.16_suppl.e13085
Abstract #
e13085
Abstract Disclosures
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