The risk of hyperprogression is lower when atezolizumab is given upfront to patients with advanced non-small cell lung cancer (NSCLC), according to an analysis published in The Oncologist.
The risk of hyperprogression was lower for patients who received atezolizumab in the first-line setting than for patients who received atezolizumab in the second-line setting or later. There was no significant difference in the risk of hyperprogression between patients who received atezolizumab in the second line and those who received it in a later line.
Researchers assessed the risk of hyperprogression among NSCLC patients using pooled data from 7 trials — BIRCH (ClinicalTrials.gov Identifier: NCT02031458), FIR (NCT01846416), POPLAR (NCT01903993), OAK (NCT02008227), IMpower130 (NCT02367781), IMpower131 (NCT02367794), and IMpower150 (NCT02366143).
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The cohort included 5152 NSCLC patients. In all, 3129 patients received treatment containing atezolizumab — 1919 in the first-line setting and 1210 in the second line or later.
In the first-line treatment cohort, 1773 patients (92%) received chemoimmunotherapy, and 146 (8%) received atezolizumab alone. In the second-line or later cohort, all patients received atezolizumab alone.
The median follow-up was 17.3 months. Among all 3129 patients treated with atezolizumab, 119 experienced hyperprogression.
The risk of hyperprogression was lower for patients treated with atezolizumab in the first-line setting than in later lines — 0.7% and 8.8%, respectively (odds ratio [OR], 0.07; 95% CI, 0.04-0.13).
Among patients treated in the first-line setting, the risk of hyperprogression was higher in patients who received atezolizumab alone rather than in combination with chemotherapy — 2.1% and 0.6%, respectively (OR, 3.70; 95% CI, 1.01-13.59).
The risk of hyperprogression with first-line atezolizumab monotherapy was lower than the risk with atezolizumab monotherapy in the second line or later (OR, 0.22; 95% CI, 0.07-0.70).
There was no significant difference in the risk of hyperprogression between patients who received second-line atezolizumab and those who received atezolizumab in a later line — 9.3% and 7.7%, respectively (OR, 1.23; 95% CI, 0.79-1.90).
The researchers noted that hyperprogression was also observed in patients who were not treated with atezolizumab.
Among patients receiving first-line treatment, there was no significant difference in the risk of hyperprogression between patients who received atezolizumab plus chemotherapy and those who received chemotherapy alone — 0.6% and 1.0%, respectively (OR, 0.55; 95% CI, 0.22-1.36).
However, among previously treated patients, the risk of hyperprogression was significantly higher with atezolizumab monotherapy than with docetaxel — 9.8% and 4.6%, respectively (OR, 2.26; 95% CI, 1.44-3.55).
The researchers evaluated predictors of hyperprogression using the 1210 patients who received atezolizumab in the second line or later. Clinical factors associated with an increased risk of hyperprogression were younger age, presence of liver metastases, and having more metastatic sites (P <.05).
Biomarkers associated with an increased risk of hyperprogression were higher neutrophil-to-lymphocyte ratio, platelet count, and C-reactive protein levels (P <.05). Neutrophil-to-lymphocyte ratio was the strongest predictor of hyperprogression (P <.001).
“Our study presents the first evidence that the risk of hyperprogression with ICI [immune checkpoint inhibitor] treatment, particularly with chemoimmunotherapy, is markedly lower in treatment-naïve patients (less than 1%) compared to previously treated patients (over 8%) with advanced non-small cell lung cancer,” the researchers wrote.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Li LX, Cappuzzo F, Matos I, et al. Low risk of hyperprogression with first-line chemoimmunotherapy for advanced non-small cell lung cancer: Pooled analysis of 7 clinical trials. Oncologist. Published online March 11, 2023. doi:10.1093/oncolo/oyad043
