In EGFR mut+ mNSCLC: Find out why your patients with exon 21 (L858R) substitution may need additional treatment options1,2
- In the United States, ~17% of patients with mNSCLC present with EGFR mutations3
- ~31% of patients have the exon 21 (L858R) substitution mutation
- ~41.5% of patients have the exon 19 deletion mutation
- Increasing evidence suggests patients with an exon 21 may have poorer outcomes than patients with an exon 192
- In patients with EGFR mut+ mNSCLC, the mutation type may impact outcomes2
- A different approach may need to be considered for your patients with exon 21 in EGFR mut+ mNSCLC4
Do you evaluate your patients' exon status when choosing treatment?

This is a newly diagnosed patient with EGFR mut+ mNSCLC5,6*
- She has an exon 21 mutation
- She had no presence of CNS metastases at diagnosis
- She has an ECOG PS of 1
- She wants to extend her PFS
*Hypothetical patient example.
This patient may be the right candidate for 1L CYRAMZA® (ramucirumab) + erlotinib5,6
SELECT IMPORTANT SAFETY INFORMATION
Hemorrhage
- CYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including Grade ≥3 hemorrhagic events. In 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade hemorrhage ranged from 13-55%. Grade 3-5 hemorrhage incidence ranged from 2-5%.
- Patients with NSCLC receiving therapeutic anticoagulation or with evidence of major airway invasion by cancer were excluded from REVEL. In addition, patients with NSCLC with a recent history of gross hemoptysis, those receiving chronic therapy with NSAIDs or other anti-platelet therapy other than once daily aspirin or with radiographic evidence of major airway or blood vessel invasion or intratumor cavitation were excluded from REVEL and RELAY; therefore the risk of pulmonary hemorrhage in these groups of patients is unknown.
- Permanently discontinue CYRAMZA in patients who experience severe (Grade 3 or 4) bleeding.
The first and only FDA-approved anti-VEGFR/
EGFR-TKI combination therapy for
EGFR mut+ mNSCLC5
Adding CYRAMZA to erlotinib increased median PFS by 7 months vs placebo + erlotinib5

- 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, respectively5
- 4 of 122 events in CYRAMZA-treated patients and 1 of 158 events in placebo-treated patients were deaths5
- The major efficacy outcome measure was PFS as assessed by the investigator RECIST v1.15
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.5,6
ORR= CR + PR; ORR does not include SD.6
28.1% of patients treated with CYRAMZA + erlotinib and 49.3% of patients treated with placebo + erlotinib had their disease progress at 1 year.7
1-Year PFS Rate (95% CI)
CYRAMZA + erlotinib (n=224) 71.9% (95% CI: 65.1, 77.6)
Placebo + erlotinib (n=225) 50.7% (95% CI: 43.7, 57.3)
SELECT IMPORTANT SAFETY INFORMATION
Gastrointestinal Perforations
- CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. In 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade and Grade 3-5 gastrointestinal perforations ranged from <1-2%.
- Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.

- The interim OS data at the time of data cutoff for the primary analysis were immature5,6
- 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 occurred5
- A final OS analysis is planned when ≥300 events have occurred6


- ORR was defined as CR + PR. ORR does not include stable disease6
- Disease progression and tumor response were assessed by investigators in accordance with RECIST v1.16
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.
Median PFS outcomes for patients with exon 21 and exon 19 mutations were consistent with the ITT population6

- 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, respectively6
- 2 of 58 events in CYRAMZA-treated patients and 1 of 74 events in placebo-treated patients were deaths8
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, respectively6
- 2 of 64 events in CYRAMZA-treated patients and 0 of 84 events in placebo-treated patients were deaths8
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.
Ask your sales representative about RELAY
1L=first-line; CI=confidence interval; CNS=central nervous system; CR=complete response; DoR=duration of response; ECOG=Eastern Cooperative Oncology Group; EGFR=epidermal growth factor receptor; HR=hazard ratio; ITT=intent-to-treat; mNSCLC=metastatic non-small cell lung cancer; mut+=mutation-positive; NSCLC=non-small cell lung cancer; 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; TKI=tyrosine kinase inhibitor; VEGFR=vascular endothelial growth factor receptor.
References: 1. Melosky B, Popat S, Gandara DR. An evolving algorithm to select and sequence therapies in EGFR mutation-positive NSCLC: a strategic approach. Clin Lung Cancer. 2018;19(1):42-50. 2. Sheng M, Wang F, Zhao Y, et al. Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a metaanalysis. Eur J Clin Pharmacol. 2016;72(1):1-11. 3. Li Y, Appius A, Pattipaka T, et al. Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non–small-cell lung cancer in the USA. PLoS One. 2019;14(1):1-14. e0209709. doi: 10.1371/journal.pone.0209709. 4. Koyama N, Watanabe Y, Iwai Y, et al. Distinct benefit of overall survival between patients with non-small-cell lung cancer harboring EGFR exon 19 deletion and exon 21 L858R substitution. Chemotherapy. 2017;62(3):151-158. 5. CYRAMZA (ramucirumab) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020. 6. 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, placebocontrolled, phase 3 trial [published online October 4, 2019]. Lancet Oncol. doi:10.1016/S1470- 2045(19)30634-5. 7. Data on File, Lilly USA, LLC, DOF-RB-US-0069. 8. Data on File, Lilly USA, LLC, DOF-RB-US-0074.