Cyramza ® (ramucirumab)

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Cyramza® (ramucirumab): Effektivitet enligt EGFR-mutationsstatus i RELAY

En fördel i progressionsfri överlevnad observerades i båda EGFR-mutationstyperna.

Detailed Information

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

Assessment of EGFR Mutation Status

All patients were assessed for EGFR mutation status prior to study enrollment and all patients were required to have an EGFR mutation of exon 19 deletion or exon 21 L858R.1 Baseline patient characteristics related to EGFR status are summarized in Table 1.

Table 1. Patient Demographics and Baseline Characteristics Related to EGFR Status1

Characteristic

RAM + ERL
n=224

PBO + ERL
n=225

EGFR mutation typea, n (%)

Exon 19 deletion

123 (55)

121 (54)

Exon 21 (L858R) mutation

101 (45)

104 (46)

EGFR testing methoda, n (%)

Therascreen® (Qiagen) and Cobas® (Roche)

96 (43)

101 (45)

Other PCR and sequencing-based methods

127 (57)

124 (55)

Abbreviations: EGFR = epidermal growth factor receptor; ERL = erlotinib; PBO = placebo; PCR = polymerase chain reaction; RAM = ramucirumab. 

a Determined by local testing.

Efficacy According to EGFR Mutation Status

Efficacy results according to EGFR mutation status are summarized in Table 2

Table 2. Efficacy Results According to EGFR Mutation Status1 

Endpoint

Median PFS, mo (95% CI)

HR (95% CI)

ITT Populationa

RAM + ERL (n=224)

19.4 (15.4-21.6)


0.591 (0.461-0.760); p<.0001

ERL + PBO (n=225)

12.4 (11.0-13.5)

Exon 19 deletion

RAM + ERL (n=123)

19.6 (15.1-22.2)


0.651 (0.469-0.903)

ERL + PBO (n=120)

12.5 (11.1-15.3)

Exon 21 (L858R) mutation

RAM + ERL (n=99)

19.4 (14.1-21.9)


0.618 (0.437-0.874)

ERL + PBO (n=105)

11.2 (9.6-13.8)

Abbreviations: EGFR = epidermal growth factor receptor; HR = hazard ratio; ITT = intent-to-treat; PBO = placebo; PFS = progression-free survival; RAM = ramucirumab. 

a Investigator-assessed PFS was the primary endpoint. 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=.002).

Kaplan Meier estimates of PFS according to EGFR mutation types are displayed in Figure 1 and Figure 2.

Figure 1. Kaplan-Meier Curve of PFS for Patients With Exon 19 Deletion1

Abbreviation: ERL = erlotinib; PBO = placebo; PFS = progression-free survival; RAM = ramucirumab.

Figure 2. Kaplan-Meier Curve of PFS for Patients With Exon 21 Mutation1

Abbreviation: ERL = erlotinib; PBO = placebo; PFS = progression-free survival; RAM = ramucirumab.

Safety Results

Safety results according to EGFR mutation status are not available; however, RELAY demonstrated that the safety profile of ramucirumab when used in combination with erlotinib was largely consistent with the known safety profiles of each of the individual treatment components in the disease setting of metastatic EGFR-mutated NSCLC. The percentage of patients discontinuing all study treatment due to an AE or an SAE was similar between treatment arms.1

Grade ≥3 TEAEs were reported in 72% of patients in the ramucirumab plus erlotinib group and 54% patients in the placebo plus erlotinib group.1 Treatment-emergent adverse events that occurred in ≥40% of patients are summarized in Table 3.

Table 3. Most Common (≥40%) TEAEs in Safety Population1

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)

Acneiform dermatitis

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 (7)c

Increased AST

92 (42)

11 (5)

58 (26)

10 (4)d

Stomatitis

92 (42)

4 (2)

82 (36)

3 (1)

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

a No grade 5 events.

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

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

d Includes 1 patient (0.4%) 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

Glossary

AE = adverse event

ECOG = Eastern Cooperative Oncology Group

EGFR = epidermal growth factor receptor

NSCLC = non-small cell lung cancer

PFS = progression-free survival

PS = performance status

SAE = serious adverse event

TEAE = treatment-emergent adverse event

Datum fӧr senaste ӧversyn 2019 M06 03

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