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Improved overall survival in patients developing endocrine toxicity during treatment with nivolumab for advanced
M Albertelli1,2, G Rossi3, E Nazzari4
1Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy. manuela.albertelli@unige.it.
Purpose:
Immune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC.
Methods:
In a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography.
Results:
An impaired thyroid function was recorded in 23.4% of patients (n = 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (p = 0.021) and multivariate analyses (p = 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (p = 0.031).
Conclusions:
Thyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.
Insights
Hypothyroidism development in advanced non-small cell lung cancer patients treated with nivolumab predicts better survival. Monitoring thyroid function and IGF-I levels is crucial for predicting nivolumab efficacy and patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Endocrinology
Background:
- Immune checkpoint inhibitors (ICPIs) targeting the PD-1/PD-L1 pathway have transformed advanced non-small cell lung cancer (NSCLC) treatment.
- Endocrine toxicities emerging during ICPI therapy have been linked to improved patient survival in some studies.
Purpose of the Study:
- To investigate the relationship between nivolumab treatment for advanced NSCLC and the incidence of immune-related endocrine adverse events (irAEs).
- To evaluate the impact of these irAEs, specifically thyroid dysfunction, on patient survival outcomes.
Main Methods:
- A prospective study involving 73 patients with previously treated advanced NSCLC receiving nivolumab monotherapy.
- Regular monitoring of thyroid autoimmunity, thyroid, adrenal, and somatotroph axes via blood samples.
- Thyroid morphology assessed through ultrasonography during treatment cycles.
Main Results:
- Thyroid dysfunction affected 23.4% of patients, with hypothyroidism being a significant outcome.
- Patients who developed hypothyroidism demonstrated significantly better overall survival (OS) compared to those who did not.
- Reduced Insulin-like Growth Factor I (IGF-I) levels, either at baseline or during follow-up, were associated with significantly reduced median survival.
Conclusions:
- Thyroid function abnormalities are common irAEs with nivolumab therapy in NSCLC patients.
- The onset of hypothyroidism serves as a positive predictive biomarker for nivolumab's antitumor efficacy.
- Low IGF-I levels may indicate a negative prognostic factor during nivolumab treatment, warranting further investigation.
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