Cyramza ® (ramucirumab)

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Cyramza® (ramucirumab): Analys av T790M i RELAY

En av de förutbestämda undersökningsändpunkterna för RELAY-studien var en analys av T790-mutationer. Preliminära bevis tyder på att ramucirumab plus erlotinib potentiellt kan försena uppkomsten av denna resistensmekanism.

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

One of the prespecified exploratory endpoints of the RELAY study was an analysis of T790 mutations.1

Exploratory Analysis of T790 Mutations

Acquired resistance to the EGFR TKIs results in TKI treatment failure and there is unmet need for treatment options that can extend EGFR TKI efficacy. The most common mechanism of resistance is through emergence of EGFR T790M mutation which occurs in 30% to 60% patients after first- and second-generation TKIs.1

EGFR T790M was assessed in liquid biopsies by Guardant360 NGS at baseline and 30-day follow-up. No patients had T790M detected at baseline by Guardant. The EGFR T790M rates at progression (n=119) were similar between treatment groups; preliminary evidence indicates the combination of ramucirumab with erlotinib may potentially delay emergence of this resistance mutation.1 At the 30-day postprogression follow-up, T790M-mutations were observed in

  • 43% of patients who received ramucirumab plus erlotinib, and

  • 47% of patients who received placebo plus erlotinib.1

Sensitivity analyses also found no difference between arms following progression.1

Cumulative T790M Rates Postprogression

Preliminary evidence suggests that ramucirumab plus erlotinib may potentially delay emergence of this resistance mechanism. The cumulative EGFR T790M rates according to total number of cycles received are summarized in Table 1.1

Table 1. Cumulative EGFR T790M Rates Postprogression According to Total Cycles Received1


4 Cyclesa

12 Cyclesa

24 Cyclesa

59 Cyclesa

RAM + ERL

PBO + ERL

RAM + ERL

PBO + ERL

RAM + ERL

PBO + ERL

RAM + ERL

PBO + ERL

T790M (+)/patients with results

0/2

0/3

2/11

5/18

4/18

18/46

19/44

35/75

T790M frequency (95% CI)

0 (0-0)

0 (0-0)

18 (5-48)

28 (13-51)

22 (9-45)

39 (26-54)

43 (30-58)

47 (36-58)

P value

NE

.677

.251

.849

Abbreviations: EGFR = epidermal growth factor receptor; ERL = erlotinib; NE = not evaluable; PBO = placebo; RAM = ramucirumab.

a Cycles completed prior to the post-progression 30-day follow-up.

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

ECOG = Eastern Cooperative Oncology Group

EGFR = epidermal growth factor receptor

NGS = next-generation sequencing

NSCLC = non-small cell lung cancer

PS = performance status

TKI = tyrosine kinase inhibitor

Datum fӧr senaste ӧversyn 2019 M06 03


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