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Published on: February 5, 2020
First cycle toxicity and survival in patients with rare cancers treated with checkpoint inhibitors
Megan Othus1,2, Sandip P Patel3, Young Kwang Chae4
1SWOG Cancer Research Network Statistical Center, Seattle, WA 98109, United States.
Background:
Associations between immune-related adverse events from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally funded basket trial (NCT02834013) for patients with rare cancers (n = 684) to evaluate associations between immune-related adverse events and overall survival and progression-free survival (PFS).
Methods:
Patients were treated with nivolumab and ipilimumab; the trial was opened at more than 1000 sites. Landmark Cox regression models were used to assess first cycle immune-related adverse event associations with PFS and overall survival.
Results:
We found that grade 1-2 treatment-related immune-related adverse events in the first cycle of therapy were associated with longer overall survival (multivariable hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.49 to 0.75; P < .001) compared with no treatment-related immune-related adverse event, while grade 3-4 immune-related adverse events were associated with shorter overall survival (HR = 1.41, 95% CI = 1.04 to 1.90; P = .025). Similar but weaker associations were observed with PFS and grade 1-2 treatment-related immune-related adverse events (HR = 0.83, 95% CI = 0.67 to 1.01; P = .067) and grade 3-4 (HR = 1.35, 95% CI = 1.02 to 1.78; P = .037) compared with no treatment-related immune-related adverse events. Grade 1-2 dermatologic toxicity was associated with improved overall survival compared with other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52 to 0.85; P = .002). There was no statistically significant overall survival difference between patients with grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other grade 1-2 toxicities.
Conclusion:
In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of immune-related adverse event in the first cycle was predictive for survival.
Insights
Immune-related adverse events (irAEs) from checkpoint inhibitors impact survival in rare cancers. Mild irAEs (grade 1-2) correlate with longer survival, while severe irAEs (grade 3-4) are linked to shorter survival.
Area of Science:
- Oncology
- Immunology
- Clinical Trials
Background:
- Checkpoint inhibitor therapy is a key treatment for many cancers.
- Immune-related adverse events (irAEs) are common side effects of these therapies.
- Prior studies on irAEs and outcomes primarily focused on common tumor types.
Purpose of the Study:
- To investigate the association between irAEs and survival outcomes in patients with rare cancers.
- To evaluate the impact of irAE severity on overall survival (OS) and progression-free survival (PFS).
Main Methods:
- Analysis of data from a federally funded basket trial (NCT02834013) including 684 patients with rare cancers.
- Treatment involved nivolumab and ipilimumab across over 1000 sites.
- Landmark Cox regression models were used to assess associations between first-cycle irAEs and survival outcomes.
Main Results:
- Grade 1-2 irAEs in the first cycle were associated with significantly longer OS (HR=0.61) compared to no irAEs.
- Grade 3-4 irAEs were associated with shorter OS (HR=1.41).
- Similar but less pronounced associations were observed for PFS; grade 1-2 dermatologic toxicity showed improved OS.
Conclusions:
- The grade of immune-related adverse events in the first cycle of checkpoint inhibitor therapy is a significant predictor of survival in patients with rare tumors.
- This finding highlights the importance of monitoring and managing irAEs in this patient population.
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