Abstract 290P
Background
ADCs are a novel effective therapy for BC. Several RCTs compared ADCs vs therapy of physician’s choice (TPC) showing impressive efficacy and leading to their accelerated approval. However, ADCs' toxicity profile can significantly affect patients' QoL long-term.
Methods
This is a systematic review and meta-analysis of RCTs of ADCs (T-DM1, Trastuzumab deruxtecan [T-DXd] and Sacituzumab-Govitecan [SG]) vs TPC (chemotherapy ± anti-HER2) in mBC with the aim of evaluating relative risk (RR) of AEs, discontinuation rate due to toxicity and impact on QoL according to EORTC QLQ-C30 scale and several health-related QoL domains (physical, emotional, social, pain, fatigue, nausea and vomiting). RRs and hazard ratios (HRs) with 95% Confidence Interval (CI) were calculated using random effects models.
Results
Seven RCTs for a total of 3, 841 patients were included. Most common any grade AEs linked to T-DM1 were thrombocytopenia and transaminitis, to T-DXd thrombocytopenia and nausea, while to SG neutropenia, diarrhea and nausea (Table). As expected, severe AEs such as interstitial lung disease (ILD) and left ventricular dysfunction (LVD) were peculiar of T-DXd. Compared to TPC, ADCs significantly delayed clinical deterioration of global health status by EORTC QLQ-C30 (HR 0.71, 95%CI 0.59-0.86), physical (HR 0.59, 95%CI 0.47-0.73), emotional (HR 0.67, 95%CI 0.59-0.75) and social functioning (HR 0.67, 95%CI 0.54-0.83), pain (HR 0.62, 95%CI 0.42-0.93) and fatigue symptoms (HR 0.72, 95%CI 0.62-0.85) but were associated with worse score for nausea and vomiting (HR 1.19, 95%CI 1.02-1.38). Table: 290P
| RR (95% CI) | |||
| T-DM1 | T-DXd | SG | |
| Neutropenia | 0.42 (0.21-0.87) | 1.39 (0.26-7.34) | 1.37 (1.22-1.54) |
| Thrombocitopenia | 7.14 (4.13-12.36) | 2.75 (1.67-4.53) | 0.43 (0.28-0.64) |
| Anemia | 0.98 (0.52-1.87) | 1.66 (1.15-2.41) | 1.40 (1.14-1.70) |
| Alopecia | 0.12 (0.04-0.40) | 3.22 (0.33-31.25) | 2.86 (2.28-3.59) |
| Fatigue | 1.04 (0.76-1.42) | 1.20 (0.99-1.47) | 1.38 (1.16-1.63) |
| Nausea | 1.15 (0.79-1.69) | 2.19 (1.69-2.83) | 1.95 (1.62-2.35) |
| Diarrhea | 0.39 (0.26-0.59) | 0.78 (0.31-1.93) | 4.00 (2.75-5.82) |
| ILD | - | 20.57 (5.09-83.08) | - |
| Increased ALT | 2.04 (1.43-2.91) | 1.18 (0.84-1.66) | - |
| LVD | 0.76 (0.26-2.16) | 2.40 (1.35-4.27) | - |
| Discontinuation rate due to AEs | 0.53 (0.21-1.33) | 1.58 (0.53-4.65) | 1.18 (0.63-2.21) |
Conclusions
This systematic review and meta-analysis provides pooled estimates to improve patient counseling on ADC-related AEs and impact on QoL, highlighting variations based on ADC type. Our results stress the need of preventing, diagnosing and managing effectively these toxicities.
Legal entity responsible for the study
Università degli Studi di Genova.
Funding
Has not received any funding.
Disclosure
M. Perachino: Financial Interests, Personal, Other, Medical advisor: Daiichi Sankyo; Other, Travel grant: Lilly, Novartis, Daiichi Sankyo. E. Blondeaux: Financial Interests, Institutional, Research Grant, Research grant to my Institution for a research project: Gilead Science. C. Molinelli: Financial Interests, Personal, Invited Speaker: Lilly; Other, Travel grants: Lilly, Menarini, Gilead; Other, Personal research grant: Fondazione Umberto Veronesi (no profit organization). C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Farma, Sanofi Avenits, Seagen, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim, Bristol Meyers Squibb, Genentech, Innoup, Millenium; Financial Interests, Personal, Other, SC: Byondis B.V., GSK, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead. All other authors have declared no conflicts of interest.