Cyramza ® (ramucirumab)

För fullständig produktresumé för Cyramza® se FASS.

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Cyramza® (ramucirumab): RAISE och effekt vid kolorektal cancer

Ramucirumab + FOLFIRI patienter hade längre medianöverlevnad och progressionsfri överlevnad jämfört med patienter som behandlats med FOLFIRI + placebo.



Information from Summary of Product Characteristics

Cyramza, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin and a fluoropyrimidine.1

Phase 3 Study

The RAISE trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated FOLFIRI and ramucirumab vs FOLFIRI and placebo in the second-line treatment of patients with mCRC who had progressed on first-line combination therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Patients were randomly assigned in a 1:1 ratio (stratified by region, KRAS mutation status, and time to progressive disease after beginning first-line treatment) to receive IV infusions of either FOLFIRI plus ramucirumab 8 mg/kg (n=536) or FOLFIRI plus placebo (n=536) once every 2 weeks.2

The primary endpoint was OS and the secondary endpoints included PFS, objective response rate (ORR) and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Randomisation was stratified by geographic region, tumour KRAS status (mutant or wild-type), and time to disease progression (TTP) after commencing first-line treatment (<6 months versus ≥6 months).2

Patients were required to have ECOG PS 0 or 1 and to have disease progression within 6 months of the last dose of first-line therapy. Patients were required to have adequate hepatic, renal and coagulation function. Patients with a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders, a recent history  of severe (Grade ≥3) bleeding or who had experienced an arterial thrombotic event (ATE) in the 12 months prior to randomisation were excluded. Patients were also excluded if they had experienced any of: an ATE, Grade 4 hypertension, Grade 3 proteinuria, a grade 3-4 bleeding event, or bowel perforation during first-line bevacizumab therapy.1,2

Efficacy Results

There was significantly greater improvement in the primary endpoint of OS in patients who received FOLFIRI plus ramucirumab than in patients who received FOLFIRI plus placebo (13.3 months vs 11.7 months, respectively, p=.0219).2The efficacy results are presented inTable 1.   Table 1. Summary of efficacy data – ITT population

Table 1.   Table 1. Summary of efficacy data – ITT population

 

Cyramza plus FOLFIRI N=536

Placebo plus FOLFIRI N=536

Overall survival, months

 

 

   Median (95% CI)

13.3 (12.4, 14.5) 

11.7 (10.8, 12.7)

   Hazard ratio (95% CI)

0.84 (0.73, 0.98)

   Stratified log-rank p-value

0.022

Progression free survival, months

 

 

   Median (95% CI)

5.7 (5.5, 6.2) 

4.5 (4.2, 5.4)

   Hazard ratio (95% CI)

0.79 (0.70, 0.90)

   Stratified log-rank p-value

<0.001

 Abbreviations: CI = confidence interval

Safety Results

Grade ≥3 TEAEs observed in ≥10% of patients who received FOLFIRI plus ramucirumab were neutropenia, fatigue, diarrhea, and hypertension.2 

The frequency and severity of the ADRs based on results from RAISE is presented in Table 2.   Table 2: ADRs reported in ≥5% of ramucirumab treated patients in RAISE

Table 2.   Table 2: ADRs reported in ≥5% of ramucirumab treated patients in RAISE






System organ

class

Frequency

ADR

Cyramza plus

FOLFIRI (N=529)

Placebo plus

FOLFIRI (N=528)

All grades

toxicity

(%)

Grade

3

toxicity

(%)

All grades

toxicity

(%)

Grade

3

toxicity

(%)

Blood and lymphatic system disorders

Very common

Neutropenia

58.8

38.4

45.6

23.3

Very common

Thrombocytopeni a

28.4

3.0

13.6

0.8

Metabolism and nutrition disorders

Common

Hypoalbuminaem ia

5.9

1.1

1.9

0.0

Vascular disorder

Very common

Hypertension

26.1

11.2

8.5

2.8

Respiratory, thoracic, and mediastinal disorders

Very common

Epistaxis

33.5

0.0

15.0

0.0

Gastrointestinal disorders

Very common

Gastrointestinal haemorrhage events

12.3

1.9

6.8

1.1

Very common

Stomatitis

30.8

3.8

20.8

2.3

Renal and urinary disorders

Very common

Proteinuriaa

17.0

3.0

4.5

0.2

Skin and subcutaneous tissue disorders

Very common

Palmar-plantar erthyrodysaesthes ia syndrome

12.9

1.1

5.5

0.4

General disorders and

administration site disorders

Very common

Peripheral oedema

20.4

0.2

9.1

0.0

a Includes cases of nephrotic syndrome.

References

1. Cyramza [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499-508. http://dx.doi.org/10.1016/S1470-2045(15)70127-0. Accompanied by: Supplementary appendix available at http://www.sciencedirect.com/science/MiamiMultiMediaURL/1-s2.0-S1470204515701270/1-s2.0-S1470204515701270-mmc1.pdf/272203/html/S1470204515701270/bba477c9410040ef01c65513f04c9c40/mmc1.pdf as a pdf file.

Glossary

5-FU = 5-fluorouracil

ADR = adverse drug reaction

ATE = arterial thromboembolic event

CI = confidence interval

ECOG = Eastern Cooperative Oncology Group

EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer quality-of-life questionnaire

FOLFIRI = irinotecan, folinic acid, and 5-fluorouracil

ITT = intent-to-treat

IV = intravenous

KRAS = Kirsten rat sarcoma viral oncogene

mCRC = metastatic colorectal cancer

ORR = objective response rate

OS = overall survival

PFS = progression-free survival

PS = performance status

QoL = quality of life

TEAE = treatment-emergent adverse event

TTP = time-to-progression

Datum fӧr senaste ӧversyn 2018 M04 25

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