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 status, and EGFR testing
method) to receive treatment with erlotinib (150 mg/day) plus
ramucirumab (10 mg/kg every 2 weeks; n=224) or placebo (10 mg/kg
every 2 weeks; n=225) until disease progression or unacceptable
toxicity.1
Postdiscontinuation
Therapy
At
the time of data cutoff, 107 (23.8%) patients were still receiving
study treatment. Of those patients in the RELAY ITT population
who discontinued study treatment, 36 (16.1%) patients in the
ramucirumab-erlotinib arm and 25 (11.1%) patients in the
placebo-erlotinib arm received no PDT.1
Per
protocol, all study treatment was stopped for RECIST progression.
Treatment beyond the point of RECIST progression was not allowed even
if there was continued benefit per investigator assessment.
Subsequent therapy was at the discretion of the investigator.1
Anticancer
PDT for the ITT population is summarized in Table
1
Table
1. Postdiscontinuation Anticancer Therapy in the RELAY ITT
Population2
|
Postdiscontinuation
Therapy
|
Ramucirumab
+ Erlotinib
(N=224)
n
(%)
|
Placebo
+ Erlotinib
(N=225)
n
(%)
|
|
Radiotherapy
|
22
(9.8)
|
33
(14.7)
|
|
Surgical
procedure
|
5
(2.2)
|
4
(1.8)
|
|
Selected
systemic therapy
|
120
(53.6)
|
156
(69.3)
|
|
ALK
inhibitor
|
|
Crizotinib
|
0
(0.0)
|
2
(0.9)
|
|
Chemotherapy
|
|
Amrubicin
|
2
(0.9)
|
0
(0.0)
|
|
Carboplatin
|
24
(10.7)
|
44
(19.6)
|
|
Carboplatin;
Etoposide
|
1
(0.4)
|
0
(0.0)
|
|
Carboplatin;
Gemcitabine
|
0
(0.0)
|
1
(0.4)
|
|
Carboplatin;
Pemetrexed
|
1
(0.4)
|
1
(0.4)
|
|
Cisplatin
|
26
(11.6)
|
30
(13.3)
|
|
Cisplatin;
Pemetrexed
|
0
(0.0)
|
2
(0.9)
|
|
Docetaxel
|
12
(5.4)
|
21
(9.3)
|
|
Etoposide
|
0
(0.0)
|
3
(1.3)
|
|
Fluorouracil;
Folinic Acid; Irinotecan
|
1
(0.4)
|
0
(0.0)
|
|
Gemcitabine
|
3
(1.3)
|
2
(0.9)
|
|
Gemcitabine;
Vinorelbine
|
1
(0.4)
|
0
(0.0)
|
|
Gimeracil;
Oteracil; Tegafur
|
3
(1.3)
|
6
(2.7)
|
|
Paclitaxel
|
7
(3.1)
|
10
(4.4)
|
|
Pemetrexed
|
42
(18.8)
|
73
(32.4)
|
|
Vinorelbine
|
3
(1.3)
|
1
(0.4)
|
|
Immunotherapy/PD-(L)1
inhibitor
|
|
Atezolizumab
|
1
(0.4)
|
1
(0.4)
|
|
Durvalumab
|
0
(0.0)
|
1
(0.4)
|
|
Nivolumab
|
5
(2.2)
|
9
(4.0)
|
|
Pembrolizumab
|
3
(1.3)
|
8
(3.6)
|
|
Spartalizumab
|
0
(0.0)
|
1
(0.4)
|
|
Immunotherapy/CTLA-4
|
|
Ipilimumab
|
1
(0.4)
|
0
(0.0)
|
|
Immunotherapy/CD73-inhibitor
|
|
Oleclumab
|
0
(0.0)
|
1
(0.4)
|
|
EGFR
antagonist
|
|
Lazertinib
|
2
(0.9)
|
0
(0.0)
|
|
EGFR-TKI
|
|
Afatinib
|
11
(4.9)
|
22
(9.8)
|
|
EGF816
|
0
(0.0)
|
1
(0.4)
|
|
Erlotinib
|
62
(27.7)
|
58
(25.8)
|
|
Gefitinib
|
11
(4.9)
|
13
(5.8)
|
|
VEGF
antibody
|
|
Bevacizumab
|
16
(7.1)
|
32
(14.2)
|
|
Ramucirumab
|
4
(1.8)
|
10
(4.4)
|
|
c-Met
inhibitor
|
|
Savolitinib
|
1
(0.4)
|
2
(0.9)
|
Abbreviations:
ALK = anaplastic lymphoma kinase; CD73 = ectonucleotidase 73; CLTA-4
= cytotoxic T-lymphocyte-associated protein 4; c-Met = hepatocyte
growth factor; EGFR = epidermal growth factor receptor; ITT =
intent-to-treat; N = number of subjects in ITT population part B; n =
number of subjects in the specified category; PD(L)1 = programmed
death-ligand 1; TKI = tyrosine kinase inhibitor; VEGF = vascular
endothelial growth factor.
Consistent
with international guidelines, treatment with a TKI beyond the point
of RECIST progression is common clinical practice if there is
continued benefit as judged by the treating physician; a practice
that may have contributed to the relatively high usage of erlotinib
as first subsequent therapy.2
Erlotinib
was the most frequently used initial PDT. Fifty-one percent and 35%
of patients in the ramucirumab-erlotinib arm vs. placebo-erlotinib
arm, respectively, received erlotinib as first PDT. Chemotherapy was
the most frequently used subsequent PDT.1
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.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Glossary
ECOG
= Eastern Cooperative Oncology Group
EGFR
= epidermal growth factor receptor
HR =
hazard ratio
ITT
= intent-to-treat
NSCLC
= non-small cell lung cancer
OS =
overall survival
PDT
= postdiscontinuation therapy
PS =
performance status
RECIST
= Response Evaluation Criteria in Solid Tumors
TKI
= tyrosine kinase inhibitor