Cyramza ® (ramucirumab)

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Cyramza® (ramucirumab): Patienter med tidigare användning av bevacizumab i REVEL

I REVEL-studien var 14% av patienterna i ramucirumab-armen och 15% av patienterna i placebo-armen tidigare behandlade med bevacizumab.

Study Design

The REVEL trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with pathologically confirmed, squamous or nonsquamous, stage IV NSCLC with disease progression during or after 1 prior platinum-based chemotherapy. Prior treatment with bevacizumab and prior maintenance therapy were allowed and all patients had an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by sex, region, PS, and previous maintenance therapy) to receive treatment with ramucirumab (10 mg/kg every 3 weeks) plus docetaxel (75 mg/m2 every 3 weeks) (n=628) or placebo plus docetaxel (75 mg/m2 every 3 weeks) (n=625) until disease progression, unacceptable toxicity, withdrawal, or death.1

In the REVEL study, 14% of patients (n=88) in the ramucirumab plus docetaxel arm, and 15% of patients (n=92) in the placebo arm received prior bevacizumab.1

Protocol Requirements Related to Prior Bevacizumab Therapy

Patients who had received prior bevacizumab as first-line or maintenance therapy were allowed to enroll. The last dose of bevacizumab must have been at least 28 days from the time of randomization.1

Efficacy

The OS and PFS results according to prior bevacizumab therapy in the REVEL study are presented in Table 1. Overall and Progression-Free Survival Results According to Prior Bevacizumab Therapy.

Table 1. Overall and Progression-Free Survival Results According to Prior Bevacizumab Therapy2

 

RAM + DOC
(n=88)

PBO + DOC
(n=92)

RAM + DOC
(n=540)

PBO + DOC
(n=533)

Prior Bevacizumab

No Prior Bevacizumab

Median OS, mo (95% CI)

10.81 (6.83-13.63)

9.00 (5.32-12.45)

10.35 (9.49-11.24)

9.17 (8.44-10.18)

HR (95% CI)

0.92 (0.64-1.31); p=NS

0.84 (0.73-0.97); p=.016

Interaction p valuea

NS

Median PFS, mo (95% CI)

4.53 (3.12-5.68)

2.83 (2.30-4.17)

4.50 (4.17-5.39)

3.06 (2.79-4.01)

HR (95% CI)

0.83 (0.61-1.13; p=NS

0.77 (0.68-0.87); p<.001

Interaction p valuea

NS

Abbreviations: DOC = docetaxel; HR = hazard ratio; NS = not significant; OS = overall survival; PBO = placebo; PFS = progression-free survival; RAM = ramucirumab. 

a P value for interaction term from a model with arm, the subgroup variable, and arm × subgroup interaction term.

Overall Response Rate

The ORR in the REVEL study according to prior bevacizumab treatment is summarized in Table 2. Overall Response in the REVEL Study According to Prior Bevacizumab Treatment. Duration of response was not calculated for this subgroup.

Table 2. Overall Response in the REVEL Study According to Prior Bevacizumab Treatment2

 

RAM + DOC
(n=88)

PBO + DOC
(n=92)

RAM + DOC
(n=540)

PBO + DOC
(n=533)

Prior Bevacizumab

No Prior Bevacizumab

Overall response ratea (95% CI) 

12.5 (6.4-21.3); p=NSb

16.3 (9.4-25.5)

24.6 (21.1-28.5); p<.001

13.1 (10.4-16.3)

Complete response, n (%) 

0

3 (0.6)

2 (0.4)

Partial response, n (%)

11 (12.5)

15 (16.3)

130 (24.1)

68 (12.8)

Abbreviations: DOC = docetaxel; NS = not significant; PBO = placebo; RAM = ramucirumab. 

a Overall response rate (complete response + partial response) was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

b P value for interaction term from a model with arm, the subgroup variable, and arm × subgroup interaction term.

Safety

No clinically relevant differences were observed in terms of adverse event profile between treatment arms according to prior bevacizumab.2 Treatment-emergent adverse events that occurred in at least 20% of patients in the ramucirumab-plus-docetaxel arm (summarized according to prior bevacizumab) are summarized in Table 3. Treatment-Emergent Adverse Events in ≥20% Patients Who Received Ramucirumab Plus Docetaxel According to Prior Bevacizumab (Safety Population).

Table 3. Treatment-Emergent Adverse Events in ≥20% Patients Who Received Ramucirumab Plus Docetaxel According to Prior Bevacizumab (Safety Population)2

Adverse Event Term, % of Patients 

RAM + DOC
(n=89)

PBO + DOC
(n=91)

RAM + DOC
(n=538)

PBO + DOC
(n=527)

Prior Bevacizumab

No Prior Bevacizumab

Fatiguea

60.7

50.5

53.7

49.9

Neutropeniaa

55.1

50.5

55.0

45.2

Neuropathya

20.2

26.4

23.6

19.4

Leukopeniaa

20.2

25.3

21.6

17.8

Anemiaa

20.2

24.2

21.0

28.8

Diarrhea

37.1

29.7

30.9

27.3

Nausea

31.5

36.3

26.2

26.0

Decreased appetite

34.8

33.0

28.1

23.5

Alopecia

20.2

23.1

26.8

25.6

Stomatitis

28.1

13.2

22.5

12.9

Dyspnea

14.6

22.0

23.2

24.5

Cough

19.1

16.5

21.6

21.4

Epistaxis

24.7

16.5

17.5

4.7

Mucosal inflammation

24.7

8.8

14.7

6.6

Peripheral edema

20.2

16.5

15.6

7.2

Constipation

20.2

20.9

15.4

16.9

Pyrexia

21.3

6.6

15.8

14.0

Abbreviations: DOC = docetaxel; PBO = placebo; RAM = ramucirumab.

a Consolidated term, based on Medical Dictionary for Regulatory Activities version 16.1.

Grade ≥3 TEAEs for patients with prior bevacizumab use observed at a higher (≥5%) incidence in the ramucirumab plus docetaxel arm than in the placebo plus docetaxel arm, respectively, were

  • febrile neutropenia (13 patients [14.6%] vs 7 patients [7.7%])

  • mucosal inflammation (5 patients [5.6%] vs 0 patients [0%]), and

  • hypertension (7 patients [7.9%] vs 1 patient [1.1%]).2

Grade ≥3 TEAEs for patients with no prior bevacizumab use observed at a higher (≥5%) incidence in the ramucirumab plus docetaxel arm than in the placebo plus docetaxel arm, respectively, were

  • neutropenia (262 patients [48.7%] vs 205 patients [38.9%]) and

  • febrile neutropenia (87 patients [16.2%] vs 55 patients [10.4%]).2

References

1. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. http://dx.doi.org/10.1016/S0140-6736(14)60845-X

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

ECOG = Eastern Cooperative Oncology Group

NSCLC = non-small cell lung cancer

ORR = overall response rate

OS = overall survival

PFS = progression-free survival

PS = performance status

TEAE = treatment-emergent adverse event

Datum fӧr senaste ӧversyn 2019 M10 30

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