Cyramza ® (ramucirumab)

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Cyramza® (ramucirumab): RELAY-studien

Cyramza i kombination med erlotinib är avsett för första linjens behandling av vuxna patienter med metastaserad icke-småcellig lungcancer med aktiverande epidermal-tillväxtfaktor-receptor (EGFR) mutationer

Cyramza® (ramucirumab): The RELAY study

Cyramza in combination with erlotinib is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations.

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

Efficacy Results

Patients treated with ramucirumab plus erlotinib had a significantly longer median PFS (investigator-assessed) than patients treated with placebo plus erlotinib (19.4 months vs 12.4 months; HR=0.59; 95% CI: 0.46-0.76; p<.0001). A consistent PFS benefit was also observed in an independent, blinded central review (HR=0.671; 95% CI: 0.518-0.869; p=.0022) as well as in both EGFR mutation types (exon 19 deletion [HR=0.65; 95% CI: 0.47-0.90; p=.0098] and exon 21 L858R [HR=0.62; 95% CI: 0.44-0.87; p=.0060]).1

The median interim OS and PFS2 have not yet been reached for either treatment group.1

Efficacy endpoint results are summarized in Table 1.

Table 1. Efficacy Endpoint Results1

Endpoint

RAM + ERL
n=224

PBO + ERL
n=225

Median PFSa, mo (95% CI)

19.4

12.4

HR (95% CI); p value

0.59 (0.46-0.76); p<.0001

1-yr PFS, % (95% CI)

71.9 (65.1-77.6)

50.7 (43.7-57.3)

ORRb (CR + PRc), % (95% CI)

76 (71-82)

75 (69-80)

CR, n (%)

3 (1)

2 (1)

PR, n (%)

168 (75)

166 (74)

SD, n (%)

42 (19)

47 (21)

DCR (CR + PR + SD), % (95% CI)

95 (92-98)

96 (93-98)

Median DOR, mo (95% CI)

18.0 (13.9-19.8)

11.1 (9.7-12.3)

HR (95% CI); p valued

0.62 (0.48-0.81); p=.0003

Abbreviations: CR = completed response; DCR = disease control rate; DOR = duration of response; ERL = erlotinib; HR = hazard ratio; ORR = objective response rate; PBO = placebo; PD = progressive disease; PFS = progression-free survival; PR = partial response; RAM = ramucirumab; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease.

a Investigator-assessed. A consistent PFS benefit was observed in the sensitivity analysis of PFS by independent, blinded central review (HR=0.671; 95% CI: 0.518-0.869; p=.0022).

b Response rate assessed using RECIST 1.1 at baseline, every 6 weeks for the first 72 weeks, and then every 12 weeks thereafter.

c Treatment difference, CR or PR, was estimated with the stratified method of Miettinen and Nurminen.

d Unstratified p value.

Safety Results

In the ramucirumab plus erlotinib group compared to the placebo plus erlotinib group

  • grade ≥3 TEAEs were reported in 72% of patients vs 54% of patients, and

  • any grade TE-SAE were reported in 29% of patients vs 21% of patients.1

Treatment-emergent adverse events that occurred in ≥20% of patients are summarized in Table 2.

Table 2. Treatment-Emergent Adverse Events Occurring in ≥20% of Patients1,2

TEAE

Any Gradea
n (%)

Grade ≥3
n (%)

Any Gradea
n (%)

Grade ≥3
n (%)

RAM + ERL
n=221

PBO + ERL
n=225

Diarrhea

155 (70)

16 (7)

160 (71)

3 (1)

Dermatitis acneiform

149 (67)

33 (15)

153 (68)

20 (9)

Paronychia

118 (53)

9 (4)

114 (51)

7 (3)

Hypertension

100 (45)

52 (24)

27 (12)

12 (5)

Increased ALT

94 (43)

19 (9)b

70 (31)

17 (8)c

Stomatitis

92 (42)

4 (2)

82 (36)

3 (1)

Increased AST

92 (42)

11 (5)

58 (26)

10 (4)d

Dry skin

83 (38)

1 (<1)

91 (40)

5 (2)

Alopecia

75 (34)

0

44 (20)

0

Proteinuria

75 (34)

6 (3)

19 (8)

0

Epistaxis

74 (33)

0

27 (12)

0

Blood bilirubin increased

68 (31)

3 (1)

70 (31)

2 (1)

Decreased appetite

57 (26)

6 (3)

47 (21)

4 (2)

Nausea

57 (26)

2 (1)

44 (20)

2 (1)

Pruritus

51 (23)

2 (1)

66 (29)

2 (1)

Peripheral edema

50 (23)

2 (1)

10 (4)

0

Cough

48 (22)

1 (<1)

35 (16)

0

Pyrexia

47 (21)

0

28 (12)

1 (<1)

Rash

39 (18)

2 (1)

54 (24)

5 (2)

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; ERL = erlotinib; ILD = interstitial lung disease; PBO = placebo; RAM = ramucirumab; TEAE = treatment-emergent adverse event.

a No deaths were reported due to TEAEs occurring in at least 20% of participants; 1 death occurred on study and was because of a pulmonary hemorrhage event of hemothorax; 1 patient in the placebo group had a fatal event of ILD more than 30 days after treatment discontinuation.

b Includes 2 patients (1%) with grade 4 events.

c Includes 3 patients (1%) with grade 4 events.

d Includes 1 patient (<1%) with a grade 4 event.

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

NSCLC = non-small cell lung cancer

OS = overall survival

PFS = progression-free survival

PFS2 = time from randomization to 2nd disease progression (defined as objective radiological or symptomatic progression after start of additional systematic anticancer treatment), or death from any cause, whichever comes first

PS = performance status

TEAE = treatment-emergent adverse event

TE-SAE = treatment-emergent serious adverse events

Datum fӧr senaste ӧversyn 2019 M11 11


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