Abstract 3836
Background
Thyroid dysfunction is one of the most common adverse effects during anti-PD-1 therapy, and alongside elevated anti-thyroid antibodies (ATAb) it is correlated with overall (OS) and progression free survival (PFS). The objective and novelty of our study was the simultaneous investigation of thyroid dysfunction and ATAbs on survival.
Methods
We included 168 patients with non-small cell lung carcinoma (n = 93), renal cell carcinoma (n = 12), and advanced and metastatic melanoma (n = 63) treated with nivolumab or pembrolizumab. TSH and fT4 serum levels were measured prior to each anti-PD-1 infusion and ATAb titers in sera, i.e. anti-TPO and anti-Tg (cut-off: 3.05 IU/ml and 22.35 IU/ml, respectively; based on median value at baseline), at baseline, and after 2 months of treatment. Thyroid dysfunction was based on TSH and fT4 and classified as subclinical or overt. Tumor progression was classified according to RECIST v1.1 and was monitored until progression, death or withdrawal of the study. Cox regression was used with correction for tumor type.
Results
Patients who acquired overt thyroid toxicity during anti-PD-1 treatment had significantly higher OS (HR = 0.17 [95% CI: 0.04-0.74]; p = 0.018) and PFS (HR = 0.38 [0.15-0.98]; p = 0.05) than patients without thyroid toxicity with one-year OS rates of 95% vs 64% and one-year PFS rates of 65% vs 33%. Moreover, patients with positive ATAb status during treatment had higher OS (HR = 0.39 [0.21-0.72]; p = 0.003) and PFS (HR = 0.52 [0.33-0.81]; p = 0.004) than patients with negative ATAb status with one-year OS rates of 83% vs 49% and PFS rates of 54% vs 20%, respectively. For 84% of patients the ATAb status at baseline was the same as during treatment. Patients with persistent positive ATAb status (48%) had higher OS (HR = 0.41 [0.19-0.89], p = 0.03) and PFS (HR = 0.54 [0.31-0.95], p = 0.03) compared to patients with persistent negative ATAb status (36%).
Conclusions
Acquired overt thyroid toxicity and positive ATAb status during anti-PD-1 treatment are associated with improved PFS and OS. Moreover, our results indicate that ATAb status at baseline is of clinical relevance for PFS and OS. If validated, these parameters may serve as a novel positive predictive markers.
Clinical trial identification
Dutch trial register: MULTOMAB, NL6828.
Editorial acknowledgement
Legal entity responsible for the study
Erasmus Medical Center.
Funding
Erasmus Medical Center.
Disclosure
A.A.M. Van der Veldt: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme. R.H. Mathijssen: Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boekringer; Research grant / Funding (institution): Cristal Therapeutics; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (self): Servier. All other authors have declared no conflicts of interest.
Resources from the same session
2316 - A 3D co-culture platform of breast cancer and patient derived immune cells to analyse the response to chemotherapy and immunotherapies
Presenter: Diana Saraiva
Session: Poster Display session 3
Resources:
Abstract
4290 - Characterization of the mechanism of action and efficacy of MEN1611 (PA799), a novel PI3K inhibitor, in breast cancer preclinical models.
Presenter: Alessio Fiascarelli
Session: Poster Display session 3
Resources:
Abstract
2167 - Neat-1: culprit lnRNA tying PIG-C, MSLN, CD80 in TNBC
Presenter: Nada Hussein
Session: Poster Display session 3
Resources:
Abstract
1829 - A novel RAF/MEK inhibitor CH5126766 in phase 1 clinical trial has an effectiveness in the combination with eribulin for the treatment of triple negative breast cancer
Presenter: Hisako Ono
Session: Poster Display session 3
Resources:
Abstract
4357 - Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer
Presenter: Eva Galan-Moya
Session: Poster Display session 3
Resources:
Abstract
5163 - Preclinical Evaluation targeting both IGF1R and IR in Triple Negative Breast Cancer
Presenter: Alex Eustace
Session: Poster Display session 3
Resources:
Abstract
832 - Monospecific antibody targeting of CDH11 inhibits epithelial-to-mesenchymal transition and represses cancer stem cell-like phenotype by up-regulating miR-335 in metastatic breast cancer, in vitro and in vivo.
Presenter: Jia-Hong Chen
Session: Poster Display session 3
Resources:
Abstract
3781 - Pharmacological screening with Chk1 inhibitors identify synergistic agents to overcome resistance to platinums in basal breast and ovarian cancer
Presenter: Ana Lucia Sanabria
Session: Poster Display session 3
Resources:
Abstract
3275 - Comparison of 11 circulating miRNAs and CA125 kinetics in ovarian cancer during first line treatment: data from the randomized CHIVA trial (a GINECO-GCIG study)
Presenter: Patrick Robelin
Session: Poster Display session 3
Resources:
Abstract
3391 - Inhibiting Ehmt2 and Ezh2 histone methyltransferases alters the immune microenvironment in a Trp53-/- murine ovarian cancer model
Presenter: Pavlina Spiliopoulou
Session: Poster Display session 3
Resources:
Abstract