KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.
- The observed hazard ratio in KEYNOTE-181 was 0.77 (95% CI, 0.63–0.96) in patients with ESCC, 0.70 (95% CI, 0.52–0.94) in patients with tumors expressing PD-L1 CPS ≥10, and 0.89 (95% CI, 0.75–1.05) in all randomized patients. On further examination in patients whose ESCC tumors expressed PD-L1 (CPS ≥10), an improvement in OS was observed among patients randomized to KEYTRUDA as compared with chemotherapy.
aBased on the Cox regression model stratified by geographic region (Asia vs ex-Asia).
- Median OS: 10.3 months with KEYTRUDA (95% CI, 7.0–13.5) vs 6.7 months with chemotherapy (95% CI, 4.8–8.6)
- Events observed: 80% (68/85) with KEYTRUDA vs 88% (72/82) with chemotherapy
PD-L1 = programmed death ligand 1; CPS = combined positive score; PD-1 = programmed death receptor-1; CI = confidence interval; HR = hazard ratio.
bBased on the Cox regression model stratified by geographic region (Asia vs ex-Asia).
CR = complete response; DOR = duration of response; ORR = objective response rate; PFS = progression-free survival; PR = partial response; Q3W = every 3 weeks.
KEYNOTE-181 was a multicenter, randomized, open-label, active-controlled trial that enrolled 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after 1 prior line of systemic treatment for advanced disease. Patients with a history of noninfectious pneumonitis that required steroids or current pneumonitis, active autoimmune disease, or a medical condition that required immunosuppression were ineligible. Patients were randomized (1:1) to receive either KEYTRUDA 200 mg every 3 weeks or investigator’s choice of any of the following chemotherapy regimens, all given intravenously: paclitaxel 80–100 mg/m2 on days 1, 8, and 15 of every 4-week cycle, docetaxel 75 mg/m2 every 3 weeks, or irinotecan 180 mg/m2 every 2 weeks. Treatment with KEYTRUDA continued until unacceptable toxicity or disease progression. Patients randomized to KEYTRUDA were permitted to continue beyond the first RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined disease progression if clinically stable until the first radiographic evidence of disease progression was confirmed at least 4 weeks later with repeat imaging. Patients treated with KEYTRUDA without disease progression could be treated for up to 24 months. Assessment of tumor status was performed every 9 weeks. The major efficacy outcome measure was OS evaluated in the following co-primary populations: patients with ESCC, patients with tumors expressing PD-L1 CPS ≥10, and all randomized patients. Additional efficacy outcome measures were PFS, ORR, and DOR, according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by blinded independent central review (BICR).
RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1.
Median age
|
65 years (33–80)
|
Age 65 or older
|
51%
|
Gender
|
84% male
|
Ethnicity
|
32% White 68% Asian
|
ECOG PS 0
|
38%
|
ECOG PS 1
|
62%
|
M1 disease
|
90%
|
M0 disease
|
10%
|
- Prior to enrollment, 99% of patients had received platinum-based treatment and 84% had also received treatment with a fluoropyrimidine.
- Thirty-three percent of patients received prior treatment with a taxane.
ECOG PS = Eastern Cooperative Oncology Group performance status.
cBased on the 7 responding patients.
KEYNOTE-180 was a multicenter, nonrandomized, open-label trial that enrolled 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least 2 prior systemic treatments for advanced disease. With the exception of the number of prior lines of treatment, the eligibility criteria were similar to and the dosage regimen identical to KEYNOTE-181. The major efficacy outcome measures were ORR and DOR according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR.
Median age
|
65 years (47–81)
|
Age 65 or older
|
51%
|
Gender
|
71% male
|
Ethnicity
|
26% White 69% Asian
|
ECOG PS 0
|
40%
|
ECOG PS 1
|
60%
|
M1 disease
|
100%
|
Testing patients for PD-L1 expression at diagnosis can help you better understand a patient’s tumor and inform treatment decisions.