Cyramza ® (ramucirumab)

För fullständig produktresumé för Cyramza® se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Cyramza® (ramucirumab): Dosminskning i RELAY

Trots det högre antalet dosjusteringar av båda läkemedlen i ramucirumab plus erlotinib-armen, var relativa mediandosintensiteten för båda läkemedlen mellan behandlingsarmarna hög och liknande.

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

Dose Adjustments

Ramucirumab could be delayed for up to 42 days, allowing for recovery from toxic effects. Additionally, three steps of dose reduction of ramucirumab were permitted (to 8 mg/kg, 6 mg/kg, and 5 mg/kg) in the event that a dose reduction criterion was fulfilled.1

Investigators were requested to refer to the erlotinib package insert or the protocol. Erlotinib could be delayed up to 3 weeks allowing for recovery from toxic effects. Two steps of dose reduction of erlotinib were permitted (to 100 mg per day and 50 mg per day) if dose reduction criterion was fulfilled.1

Dose modifications were permitted for all patients in RELAY part B in the setting of non-life-threatening and reversible grade 3 clinical AEs considered to be at least possibly related to ramucirumab/placebo. Adverse events had to be resolved to grade ≤1 or pretreatment baseline within 1 treatment cycle (approximately 2 weeks).2

Dose reductions of ramucirumab or placebo were defined as total number of reduction steps considering the intended dose level before each infusion. Dose reductions of erlotinib were defined as total number of reduction steps considering the intended dose level.2

Dose delays of ramucirumab or placebo were defined as total number of treatments reported as delayed that were administered >3 days but ≤11 days beyond a scheduled infusion where treatment was not given.2

Dose omissions of ramucirumab or placebo were defined as total number of treatments reported as omitted or delayed that were administered >11 days beyond a scheduled infusion where treatment was not given. Dose omissions of erlotinib were defined as total number of doses withheld as 1 per omission interval.2

A higher proportion of patients in ramucirumab plus erlotinib group than the placebo plus erlotinib group had dose adjustments of any study drug. Most patients with a dose modification of ramucirumab or placebo had 1 or more dose delays.1 Dose adjustments are summarized in Table 1.

Table 1. Summary of Dose Adjustments in the Safety Population in RELAY2

 

Ramucirumab + Erlotinib

N=221

n (%)

Placebo + Erlotinib

N=225

n (%)

 

Ramucirumab

Erlotinib

Placebo

Erlotinib

Patients with at least 1 dose adjustment

168 (76.0)

143 (64.7)

133 (59.1)

134 (59.6)

Patients with a dose reduction

23 (10.4)

99 (44.8)

4 (1.8)

96 (42.7)

1 dose reduction

14 (6.3)

64 (29.0)

3 (1.3)

71 (31.6)

2 dose reductions

7 (3.2)

31 (14.0)

1 (0.4)

22 (9.8)

3 dose reductions

2 (0.9)

4 (1.8)

0

3 (1.3)

Reasons leading to dose reductions

AEs

23 (10.4)

96 (43.4)

4 (1.8)

93 (41.3)

Others

0

10 (4.5)

0

10 (4.4)

Patients with a dose delay

147 (66.5)

NA

121 (53.8)

NA

1 dose delay

50 (22.6)

NA

50 (22.2)

NA

2 dose delays

33 (14.9)

NA

31 (13.8)

NA

3 dose delays

64 (29.0)

NA

40 (17.8)

NA

Reasons leading to dose delays

AEs

140 (63.3)

NA

102 (45.3)

NA

Scheduling conflict

32 (14.5)

NA

37 (16.4)

NA

Patients with a dose omission

62 (28.1)

119 (53.8)

28 (12.4)

118 (52.4)

1 dose omission

50 (22.6)

51 (23.1)

18 (8.0)

54 (24.0)

2 dose omissions

8 (3.6)

24 (10.9)

3 (1.3)

29 (12.9)

3 dose omissions

4 (1.8)

44 (19.9)

7 (3.1)

35 (15.6)

Reasons leading to dose omission

AEs

48 (21.7)

116 (52.5)

20 (8.9)

113 (50.2)

Others

17 (7.7)

34 (15.4)

11 (4.9)

30 (13.3)

Abbreviations: AEs = adverse events; NA = not available (dose delays were not captured for erlotinib).

Adverse Events Leading to Dose Adjustments

A similar proportion of patients with dose adjustments in the ramucirumab plus erlotinib group and placebo plus erlotinib group had dose reductions of erlotinib due to TEAEs. The most common TEAE leading to erlotinib dose reduction was dermatitis acneiform followed by increased alanine aminotransferase.1 Adverse events leading to dose adjustments are summarized in Table 2.

Table 2. Treatment-Emergent Adverse Events Occurring in ≥5% of Patients Leading to Dose Adjustment in the Safety Population in RELAY2

 

Ramucirumab + Erlotinib

N=221

n (%)

Placebo + Erlotinib

N=225

n (%)

MedDRA Preferred Term

Any Grade

Grade ≥3

Any Grade

Grade ≥3

Patients with any TEAEs leading to ramucirumab or placebo dose adjustment

154 (69.7)

40 (18.1)

109 (48.4) 

21 (9.3)

Blood bilirubin increased

49 (22.2)

2 (0.9)

52 (23.1)

1 (0.4)

Proteinuria

27 (12.2)

5 (2.3)

0

0

Alanine aminotransferase increased

25 (11.3)

4 (1.8)

16 (7.1)

4 (1.8)

Neutrophil count decreased

13 (5.9)

1 (0.5)

10 (4.4)

0

Platelet count decreased

13 (5.9)

0

0

0

Aspartate aminotransferase increased

11 (5.0)

1 (0.5)

4 (1.8)

1 (0.4)

Hypertension

11 (5.0)

5 (2.3)

4 (1.8)

3 (1.3)

TEAEs leading to dose reduction

23 (10.4)

2 (0.9)

4 (1.8)

2 (0.9)

Proteinuria

18 (8.1)

0

0

0

TEAEs leading to dose delay

137 (62.0)

25 (11.3)

100 (44.4)

14 (6.2)

Blood bilirubin increased

46 (20.8)

0

46 (20.4)

1 (0.4)

Alanine aminotransferase increased

21 (9.5)

2 (0.9)

16 (7.1)

4 (1.8)

Proteinuria

16 (7.2)

1 (0.5)

0

0

Platelet count decreased

12 (5.4)

0

0

0

Aspartate aminotransferase increased

11 (5.0)

1 (0.5)

3 (1.3)

0

Neutrophil count decreased

11 (5.0)

0

10 (4.4)

0

TEAEs leading to dose omission

48 (21.7)

17 (7.7)

20 (8.9)

5 (2.2)

Proteinuria

15 (6.8)

5 (2.3)

0

0

Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities; TEAEs = treatment-emergent adverse events.

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

AE = adverse event

ECOG = Eastern Cooperative Oncology Group

EGFR = epidermal growth factor receptor

NSCLC = non-small cell lung cancer

PS = performance status

TEAE = treatment-emergent adverse event

Datum fӧr senaste ӧversyn 2019 M10 16


Kontakta Medicinsk Information på Lilly

Kontakta oss på telefon

Kontorstid vardagar 9.00-17.00

Eller så kan du

Skriv din fråga till oss