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Cyramza ® (ramucirumab)
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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
Enrollment According to Region
Details on enrollment according to stratification by geographic region in the RELAY study are summarized in Table 1.
Table 1. Geographic Regions Represented in RELAY2
|
Geographic Region |
Ramucirumab
+ Erlotinib n (%) |
Placebo
+ Erlotinib n (%) |
Total n (%) |
|
East Asiaa |
166 (74.1) |
170 (75.6) |
336 (74.8) |
|
Otherb |
58 (25.9) |
55 (24.4) |
113 (25.2) |
a East Asia includes: South Korea, Hong Kong, Japan, and Taiwan.
b Other includes: Canada, France, Germany, Italy, Romania, Spain, Turkey, United States, and United Kingdom.
Efficacy According to Region
A PFS treatment benefit with ramucirumab plus erlotinib was observed in the predefined region subgroups.3 Efficacy results according to region subgroups are summarized in Table 2.
Table 2. Efficacy Results According to Region in RELAY2
|
|
Ramucirumab
+ Erlotinib |
Placebo
+ Erlotinib |
Ramucirumab
+ Erlotinib |
Placebo
+ Erlotinib |
|
East Asia |
Other |
|||
|
Median PFSa, mo (95% CI) |
19.4 (15.2-21.9) |
12.5 (11.1-13.9) |
20.6 (14.7-26.0) |
10.9 (8.3-19.4) |
|
HRb (95% CI); p valuec |
0.636 (0.485-0.833); p=.0009 |
0.605 (0.362-1.010); p=.0523 |
||
|
Interaction p valued |
p=.9752 |
|||
Abbreviations: HR = hazard ratio; PFS = progression-free survival.
a Estimated using the Kaplan-Meier method.
b Hazard ratio and 95% CI (Wald) were estimated from unstratified Cox model.
c Two-sided p value from unstratified log-rank test.
d Wald test of treatment-by-subgroup interaction from unstratified Cox model.
Safety According to Region
In RELAY, the safety profile within the region subgroups between treatment arms was consistent with that observed in the overall safety population.2 Any grade TEAEs that occurred in at least 20% of patients in the ramucirumab arm (summarized by region) are summarized in Table 3.
Table 3. Any Grade TEAEs in ≥20% of Patients Who Received Ramucirumab Plus Erlotinib in the Region Subgroups in RELAY2
|
TEAE, % of Patients |
Ramucirumab
+ Erlotinib |
Placebo
+ Erlotinib |
Ramucirumab
+ Erlotinib |
Placebo
+ Erlotinib |
|
East Asia |
Other |
|||
|
Dermatitis acneiform |
78.7 |
77.6 |
35.1 |
38.2 |
|
Diarrhea |
68.3 |
69.4 |
75.4 |
76.4 |
|
Paronychia |
61.0 |
58.8 |
31.6 |
25.5 |
|
ALT increased |
46.3 |
35.3 |
31.6 |
18.2 |
|
Stomatitis |
45.7 |
36.5 |
29.8 |
36.4 |
|
AST increased |
44.5 |
30.0 |
33.3 |
12.7 |
|
Hypertension |
42.7 |
11.8 |
52.6 |
12.7 |
|
Proteinuria |
37.8 |
7.6 |
22.8 |
10.9 |
|
Dry skin |
37.2 |
38.8 |
38.6 |
45.5 |
|
Alopecia |
35.4 |
14.7 |
29.8 |
34.5 |
|
Epistaxis |
35.4 |
12.9 |
28.1 |
9.1 |
|
Blood bilirubin increased |
33.5 |
35.3 |
22.8 |
18.2 |
|
Nausea |
26.2 |
17.6 |
24.6 |
25.5 |
|
Decreased appetite |
25.6 |
18.8 |
26.3 |
27.3 |
|
Peripheral edema |
22.6 |
4.7 |
22.8 |
3.6 |
|
Pyrexia |
22.0 |
14.7 |
19.3 |
5.5 |
|
Malaise |
20.7 |
11.8 |
N/A |
N/A |
|
Cough |
15.2 |
12.4 |
40.4 |
25.5 |
|
Rash |
10.4 |
16.5 |
38.6 |
47.3 |
|
Pruritus |
19.5 |
26.5 |
33.3 |
38.2 |
|
Fatigue |
4.9 |
8.2 |
31.6 |
23.6 |
|
Asthenia |
3.7 |
0 |
21.1 |
25.5 |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; N/A = not available; TEAE = treatment-emergent adverse event.
1. Nakagawa K, Garon E, Seto T, et al. RELAY: A multicenter, double-blind, randomized, phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor (EGFR) mutation-positive metastatic non-small cell lung cancer (NSCLC). Talk presented at: 55th Annual Meeting of the American Society of Clinical Oncology (ASCO); May 31-June 4, 2019; Chicago, IL. https://meetinglibrary.asco.org/record/173373/abstract
2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3. 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
Glossary
ECOG = Eastern Cooperative Oncology Group
EGFR = epidermal growth factor receptor
NSCLC = non-small cell lung cancer
PFS = progression-free survival
PS = performance status
TEAE = treatment-emergent adverse event
Datum fӧr senaste ӧversyn 2019 M10 24