
Adding CYRAMZA® (ramucirumab) to erlotinib increased median PFS
by 7 months vs placebo + erlotinib1

- The percentage of events at the time of analysis was 55% (122 patients) and 70% (158 patients) in the CYRAMZA + erlotinib and placebo + erlotinib treatment arms, respectively1
- 4 of 122 events in CYRAMZA-treated patients and 1 of 158 events in placebo-treated patients were deaths1
- The major efficacy outcome measure was PFS as assessed by the investigator RECIST v1.11
28.1% of patients treated with CYRAMZA + erlotinib and 49.3% of those treated with placebo + erlotinib had their disease progress at 1 year2
The RELAY trial evaluated the efficacy and safety of CYRAMZA + erlotinib vs placebo + erlotinib in previously untreated patients with EGFR mut+ mNSCLC. Major outcome measure was PFS. Supportive outcome measures included OS, ORR, and DoR. Patients were stratified by EGFR mutation status (exon 21 vs exon 19), geographic region (East Asia vs other), gender, and local EGFR testing method (therascreen® and cobas® vs other PCR and sequencing-based methods). All patients were required to have ECOG PS 0 or 1. Patients were randomized 1:1 to receive CYRAMZA 10 mg/kg (n=224) or placebo (n=225) every 2 weeks + erlotinib 150 mg/day.1,3
ORR=CR+PR; ORR does not include SD.3
For patients on CYRAMZA + erlotinib who had a response, the median DoR was 18.0 months with CYRAMZA + erlotinib vs 11.1 months with placebo + erlotinib1,3

- The percentage of events at the time of analysis was 59% (101 patients) and 76% (128 patients) in the CYRAMZA + erlotinib and placebo + erlotinib treatment arms, respectively3
DoR was a prespecified secondary efficacy endpoint. DoR was not powered or controlled for type 1 error, and treatment differences observed cannot be regarded as statistically significant.
SELECT IMPORTANT SAFETY INFORMATION
Arterial Thromboembolic Events (ATEs)
- Serious, sometimes fatal, ATEs, including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia, occurred across clinical trials. In 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade ATE was 1-3%. Grade 3-5 ATE incidence was <1-2%.
- Permanently discontinue CYRAMZA in patients who experience an ATE.

- The interim OS data at the time of data cutoff for the primary analysis were immature1,3
- At the time of the final analysis of PFS, OS data were not mature as only 26% of planned events for the final analysis had occurred1
- A final OS analysis is planned when ≥300 events have occurred3

- ORR was defined as CR + PR. ORR does not include stable disease3
- Disease progression and tumor response were assessed by investigators in accordance with RECIST v1.13
ORR was a prespecified secondary efficacy endpoint. ORR was not powered or controlled for type 1 error, and treatment differences observed cannot be regarded as statistically significant.
Disease Control (DC)* was 95% in the CYRAMZA + erlotinib arm and 96% in the placebo + erlotinib arm.3
Prespecified Supportive Outcome Measure: DC3*
CYRAMZA + erlotinib (n=213/224)
95% (95% CI: 92, 98)
CR=1% (n=3)
PR=75% (n=168)
SD=19% (n=42)
Placebo + erlotinib (n=215/225)
96% (95% CI: 93, 98)
CR=1% (n=2)
PR=74% (n=166)
SD=21% (n=47)
*DC was defined as CR + PR + SD.
DC was a prespecified secondary efficacy endpoint. This endpoint was not powered or controlled for type 1 error, and treatment differences observed cannot be regarded as statistically significant.
SELECT IMPORTANT SAFETY INFORMATION
Hypertension
- An increased incidence of severe hypertension occurred in patients receiving CYRAMZA. Across five clinical studies, excluding RELAY, in 1916 patients with various cancers treated with CYRAMZA, the incidence of all Grade hypertension ranged from 11-26%. Grade 3-5 hypertension incidence ranged from 6-15%. In 221 patients with NSCLC receiving CYRAMZA in combination with erlotinib in the RELAY study, the incidence of new or worsening hypertension was higher (45%), as was the incidence of Grade 3-5 hypertension (24%). Of the patients experiencing new or worsening hypertension in RELAY (N=100 CYRAMZA and erlotinib; N=27 placebo and erlotinib), 13% of those treated with CYRAMZA and erlotinib required initiation of 3 or more antihypertensive medications compared to 4% of patients treated with placebo and erlotinib.
- Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every two weeks or more frequently as indicated during treatment. Withhold CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA for medically significant hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.
Median PFS outcomes for patients with exon 21 (L858R) substitution and exon 19 deletion were consistent with the ITT population3

- The percentage of events at the time of analysis was 58.6% (58 patients) and 70.5% (74 patients) in the CYRAMZA + erlotinib and placebo + erlotinib treatment arms, respectively3
- 2 of 58 events in CYRAMZA-treated patients and 1 of 74 events in the placebo-treated patients were deaths4
The RELAY trial was not adequately powered or error controlled for subgroup analysis. Treatment differences observed in this subgroup cannot be regarded as statistically significant.

- The percentage of events at the time of analysis was 52.0% (64 patients) and 70.0% (84 patients) in the CYRAMZA + erlotinib and placebo + erlotinib treatment arms, respectively3
- 2 of 64 events in CYRAMZA-treated patients and 0 of 84 events in the placebo-treated patients were deaths4
The RELAY trial was not adequately powered or error controlled for subgroup analysis. Treatment differences observed in this subgroup cannot be regarded as statistically significant.
SELECT IMPORTANT SAFETY INFORMATION
Infusion-Related Reactions (IRR)
- IRR, including severe and life-threatening IRR, occurred in CYRAMZA clinical trials. Symptoms of IRR included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. In 2137 patients with various cancers treated with CYRAMZA in which premedication was recommended or required, the incidence of all Grade IRR ranged from <1- 9%. Grade 3-5 IRR incidence was <1%.
- Premedicate prior to each CYRAMZA infusion. Monitor patients during the infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Reduce the infusion rate by 50% for Grade 1-2 IRR. Permanently discontinue CYRAMZA for Grade 3- 4 IRR.
Prespecified subgroup analyses of PFS5

†East Asia includes South Korea, Hong Kong, Japan, and Taiwan, and Other includes Canada, France, Germany, Italy, Romania, Spain, Turkey, the United States, and the United Kingdom.
‡Testing method for 1 patient was missing on the CRF. Patient was stratified by other PCR and sequencing-based method in IWRS.
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These analyses were not adjusted for multiplicity or powered to detect the effect of CYRAMZA + erlotinib within subgroups. Therefore, no conclusions of statistical significance can be drawn.
Consider CYRAMZA + erlotinib for your patients with EGFR mut+ mNSCLC with an exon 21 or exon 19 mutation
Ask your sales representative about RELAY
CI=confidence interval; CR=complete response; CRF=case report form; DoR=duration of response; ECOG=Eastern Cooperative Oncology Group; EGFR=epidermal growth factor receptor; HR=hazard ratio; ITT=intent-to-treat; IWRS=interactive web-response system; mNSCLC=metastatic non-small cell lung cancer; mut+=mutation-positive; ORR=overall response rate; OS=overall survival; PCR=polymerase chain reaction; PFS=progression-free survival; PR=partial response; PS=performance status; RECIST=Response Evaluation Criteria in Solid Tumors; SD=stable disease.
References: 1. CYRAMZA (ramucirumab) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020. 2. Data on File, Lilly USA, LLC, DOF-RB-US-0069. 3. Nakagawa K, Garon EB, Seto T, et al; for RELAY Study Investigators. 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 [published online October 4, 2019]. Lancet Oncol. doi:10.1016/S1470-2045(19)30634-5. 4. Data on File, Lilly USA, LLC, DOF-RB-US-0074. 5. Data on File, Lilly USA, LLC, DOF-RB-US-0071.