ASCO 2018: Elevated Serum PD-L1 May Identify Patients With HER2–Positive Metastatic Breast Cancer Who Would Benefit From the Addition of a Checkpoint Inhibitor
June 4, 2018—Chicago—Elevated serum PD-L1 may identify patients with HER2–positive metastatic breast cancer who would benefit from the addition of a checkpoint inhibitor.
This conclusion, based on results of the phase 3 Canadian Cancer Trials Group MA.31 trial, was presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, from June 1 to 5.
Allan Lipton, MD, Suhail M. Ali, MD, and Kim Leitzel, MD, of Penn State Hershey Medical Center, Pennsylvania, explained that in the MA.31 trial, the lapatinib–taxane combination led to shorter progression-free survival than trastuzumab–taxane in HER2–positive metastatic breast cancer.
Dr. Lipton and colleagues reported the positive prognostic utility of pretreatment serum PD-L1 in 2017, in 63 trastuzumab-treated patients.
In the present study, Dr. Lipton’s team set out to evaluate the prognostic utility of pretreatment serum PD-L1 testing in the trastuzumab arm of MA.31.
“We undertook the study,” Dr. Lipton told Elsevier’s PracticeUpdate, “to determine whether checkpoint inhibition of the immune system exerts any effect on the response to trastuzumab therapy.”
MA.31 accrued 652 centrally and/or locally identified HER2–positive patients. In the trastuzumab arm, 186 patients had available pretreatment serum. The Ella immunoassay platform (ProteinSimple, San Jose, California) was used to quantitate serum PD-L1. Stratified stepwise forward Cox multivariate analysis was used to calculate progression-free and overall survival.
In univariate analysis for progression-free survival, serum PD-L1 was not a significant biomarker for progression-free survival. In univariate analysis for overall survival, higher serum PD-L1 was a significant biomarker for shorter overall survival:
- Continuous PD-L1: hazard ratio 3.86, P = .044
- Quartiles of PD-L1: hazard ratio 1.55, P = .002
- Median cut point PD-L1: hazard ratio 2.16, P = .014
Multivariate analysis for overall survival included 14 covariates:
- Age
- Race
- Eastern Cooperative Oncology Group status
- Anthracyclines
- Other chemotherapies
- Endocrine therapies
- Radiotherapies
- Other prior adjuvant therapies
- Disease status
- Estrogen receptor status
- Progesterone receptor status
- Ki67 (log transformed)
- CK5
- EGFR
- Serum PD-L1
Elevated serum PD-L1 was a significant independent covariate (continuous PD-L1: hazard ratio 22.7, P = .001; median cut point PD-L1: hazard ratio 2.91, P = .0061).
Dr. Lipton concluded that in the Canadian Cancer Trials Group MA.31 trial, elevated pretreatment serum PD-L1 was associated with a shorter overall but not progression-free survival with trastuzumab treatment. Immune evasion by the tumor may reduce the effectiveness of trastuzumab therapy.
“There appears to be a subgroup of patients with HER2–positive metastatic breast cancer with high serum PD-L1 levels who do less well on trastuzumab treatment," Dr. Lipton said
“Going forward, “he added, “it would be interesting to see how these patients respond to therapy with trastuzumab + a PD-1 or PD-L1 inhibitor.”
Click on any of these tags to subscribe to Topic Alerts. Once subscribed, you can get a single, daily email any time PracticeUpdate publishes content on the topics that interest you.
Visit your Preferences and Settings section to Manage All Topic Alerts