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Published on: February 8, 2018
Evaluation of immune checkpoint inhibitor efficacy for solid tumors with CD274 (PD-L1 gene) amplification identified
Tomohiro Nakayama1,2, Takayuki Takahama3,4, Yasutaka Chiba5
1Medical Oncology, Kishiwada City Hospital, Kishiwada, Japan.
Insights
Programmed cell death-ligand 1 gene (CD274) amplification in solid tumors may predict response to immune checkpoint inhibitors (ICIs). This largest analysis to date suggests CD274 amplification could be a biomarker for ICI efficacy.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Amplification of the programmed cell death-ligand 1 gene (CD274) is prevalent in lymphomas and a potential biomarker for immune checkpoint inhibitor (ICI) treatment in solid tumors.
- The efficacy of ICIs in solid tumors with CD274 amplification identified by comprehensive genomic profiling (CGP) remained unclear.
Purpose of the Study:
- To examine the efficacy of ICIs for solid tumors with CD274 amplification identified by CGP.
Main Methods:
- Retrospective analysis of 60,155 CGP results from a national database.
- Included patients treated with ICIs alone.
- Matched 48 CD274-amplified patients with 170 CD274-non-amplified patients (1:4 ratio) based on tumor type, histology, treatment, and age.
Main Results:
- Overall survival (OS) was similar between groups (median 22.1 vs. 26.3 months).
- Time to next treatment (TTNT) tended to be longer in the CD274-amplified group (median 16.5 vs. 14.0 months).
- Objective response rate (33.3% vs. 18.4%) and disease control rate (63.9% vs. 41.1%) were higher in the CD274-amplified group.
Conclusions:
- This study represents the largest cohort of solid tumors with CD274 amplification.
- CD274 amplification identified by CGP may be associated with ICI treatment outcomes in solid tumors.
- CD274 amplification may serve as a predictive biomarker for ICI efficacy in solid tumors.
Background:
Amplification of the programmed cell death-ligand 1 gene (CD274) is highly prevalent and associated with a high response rate to immune checkpoint inhibitors (ICIs) in lymphomas, and is also a potential biomarker for ICI treatment of solid tumors. However, the efficacy of ICIs for solid tumors with CD274 amplification identified by comprehensive genomic profiling (CGP) has been unclear. We here examined ICI efficacy for solid tumors with CD274 amplification identified by CGP in a national database.
Methods:
We retrospectively analyzed data from the Center for Cancer Genomics and Advanced Therapeutics database containing 60,155 CGP test results for individuals with solid tumors. Only clinical data from patients treated with ICIs alone (not those undergoing concomitant therapy with molecularly targeted or cytotoxic chemotherapeutic agents) were evaluated. We matched 48 patients in the CD274 amplification-positive group with 170 patients in the CD274 amplification-negative group in a 1:4 ratio based on tumor type, histology, treatment, and age. Overall survival (OS), time to next treatment (TTNT), and response rate were evaluated as treatment outcomes in the two groups.
Results:
OS was similar in the CD274-amplified and matched CD274-non-amplified groups (median of 22.1 vs 26.3 months, respectively; HR of 0.92 with a 95% CI of 0.55 to 1.54; p=0.075). TTNT tended to be longer in the CD274-amplified group than in the matched CD274-non-amplified group (median of 16.5 vs 14.0 months; HR of 0.63 with a 95% CI of 0.37 to 1.08; p=0.091). The objective response rate was 33.3% and 18.4% (difference of 14.9%, with a 95% CI of -0.2% to 31.6%), and the disease control rate was 63.9% and 41.1% (difference of 22.8%, with a 95% CI of 5.1% to 40.4%), in the CD274-amplified and matched CD274-non-amplified groups, respectively.
Conclusions:
The number of patients with solid tumors positive for CD274 amplification in this analysis is the largest to date, and our results suggest that such gene amplification may be associated with the outcome of ICI treatment in such individuals. CD274 amplification identified by CGP may therefore be a predictor of ICI efficacy for solid tumors.
Trial Registration Number:
UMIN000029779.
