Cyramza ® (ramucirumab)

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Cyramza® (ramucirumab): Efficacy and Safety by Region in RELAY

In RELAY, PFS treatment benefit for ramucirumab plus erlotinib was observed in the predefined region subgroups and the safety profile within the region subgroups, between treatment arms was consistent with that observed in the overall safety population.

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

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=224) 

n (%)

Placebo + Erlotinib
(N=225)

n (%)

Total
(N=449)

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
(n=166)

Placebo + Erlotinib
(n=170)

Ramucirumab + Erlotinib
(n=58)

Placebo + Erlotinib
(n=55)

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
(n=164)

Placebo + Erlotinib
(n=170)

Ramucirumab + Erlotinib
(n=57)

Placebo + Erlotinib
(n=55)

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.

References

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

Date of Last Review: October 24, 2019

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