Study
Design
The
RELAY trial was a phase 3, global, multicenter, randomized,
double-blind, placebo-controlled trial in patients (N=449) with
previously untreated EGFR mutation-positive, metastatic NSCLC. All
patients had an EGFR mutation of exon 19 deletion or exon 21 L858R
and an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1
ratio (stratified by sex, region, EGFR mutation type, and EGFR
testing method) to receive treatment with erlotinib (150 mg/day) plus
ramucirumab (10 mg/kg every 2 weeks; n=224) or placebo (every 2
weeks; n=225) until disease progression or unacceptable toxicity.1
Assessment
of Patient-Focused Outcomes
Assessment
Interval
Patient-focused
outcomes were evaluated using ECOG PS, LCSS, and EQ-5D-5L.2
ECOG
PS was assessed by the clinician
at
baseline
before
every cycle
at
the end of treatment, and
at
the 30-day follow-up visit.2
LCSS
and EQ-5D-5L questionnaires were completed by the patients at the
beginning of the clinic visit
ECOG
PS Assessment
Time-to-deterioration
in ECOG PS was
a
prespecified exploratory endpoint
defined
as the time from randomization to the first observation of ECOG PS
≥2
analyzed
using the Kaplan-Meier method, and
compared
using an unstratified log rank test.2
LCSS
and EQ-5D-5L Assessment
Time-to-deterioration
in LCSS was
a
prespecified secondary endpoint
defined
as the time from date of randomization until the date of the first
≥15 mm increase from baseline, and
estimated
with Kaplan-Meier and Cox regression.2
The
EQ-5D-5L questionnaire was
a
prespecified secondary endpoint, and
mean
scores were summarized by cycle/visit.3
Mean
changes from baseline in EQ-5D-5L/LCSS scores were estimated using
Mixed Effect Model Repeat Measurement regression by comparing with
baseline scores.2,3
Assessment
Compliance
Patient
compliance for both LCSS and EQ-5D-5L completion across all time
points was high, the rates being
95.7%
in the ramucirumab plus erlotinib arm and 96.7% in the placebo plus
erlotinib arm for the LCSS, and
96.1%
in the ramucirumab plus erlotinib arm and 96.6% in the placebo plus
erlotinib arm for the EQ-5D-5L.2
At
the 30-day safety follow-up visit, compliance rates were
74.4%
in the ramucirumab plus erlotinib arm and 79.1% in the placebo plus
erlotinib arm for the LCSS, and
74.4%
in the ramucirumab plus erlotinib arm and 79.7% in the placebo plus
erlotinib arm for EQ-5D-5L.2
Patient-Reported
Outcome Results
ECOG
PS
The
majority of patients in both arms maintained an ECOG PS of 0 or 1
(94% in both arms); therefore, TTD analysis was not feasible at the
time of data cut-off.2
LCSS
and EQ-5D-5L
Time-to-deterioration
in LCSS total score and ASBI was similar between treatment arms (LCSS
total score: HR=0.962; 95% CI: 0.690-1.343; ASBI: HR=1.012; 95% CI:
0.732-1.400). Hemoptysis was the only LCSS item for which the TTD was
different between arms and favored the erlotinib plus placebo arm
(HR=1.987; 95% CI: 1.206-3.275).2
The
mean EQ-5D-5L Index Scores across treatment cycles were similar
between treatment arms and remained constant within arms over time;
however, a decline in the mean scores for both treatment arms was
observed at the 30-day follow-up visit.2
References
1.
Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in
patients with untreated, EGFR-mutated, advanced non-small-cell lung
cancer (RELAY): a randomised, double-blind, placebo-controlled, phase
3 trial. Lancet Oncol. 2019;20(12):1655-1669.
https://doi.org/10.1016/S1470-2045(19)30634-5
2.
Yoh K, Atagi S, Reck M, et al. Patient-reported outcomes in RELAY, a
phase 3 trial of ramucirumab plus erlotinib versus placebo plus
erlotinib in untreated EGFR-mutated metastatic non-small-cell lung
cancer. Curr Med Res Opin. 2020;36(10):1667-1665.
https://doi.org/10.1080/03007995.2020.1808781
3.
Yoh K, Atagi S, Reck M, et al. Patient-focused outcomes in RELAY, a
phase 3 trial of ramucirumab plus erlotinib versus placebo plus ERL
in untreated EGFR-mutated metastatic NSCLC. Talk presented at: 5th
Annual Meeting of the European Society of Medical Oncology Asia (ESMO
Asia); November 22-24, 2019; Singapore, Singapore.
Glossary
ASBI
= average symptom burden index
ECOG
= Eastern Cooperative Oncology Group
EGFR
= epidermal growth factor receptor
EQ-5D-5L
= EuroQoL five-dimension, five-level health status questionnaire
HR =
hazard ratio
LCSS
= Lung Cancer Symptom Scale
NSCLC
= non-small cell lung cancer
PS =
performance status
QOL
= quality of life
TTD
= time-to-deterioration