NSCLC: Sensitizing EGFR mutation positive…Erlotinib + ramucirumab...the NCCN NSCLC panel recommends erlotinib/ramucirumab as a first-line therapy option for patients with EGFR-positive metastatic NSCLC…

Ramucirumab (a human IgG1 VEGFR2 antagonist) in combination with erlotinib (versus erlotinib in combination with placebo) led to superior PFS (19.4 versus 12.4 months, HR 0.59, 95% CI 0.46–0.76, P<0.0001) in first-line EGFR-mutated NSCLC in a phase III trial.

Eligible patients with EGFR+ mNSCLC were randomized 1 : 1 to ERL (150 mg/day) plus RAM (10 mg/kg)/PBO every 2 weeks….RAM + ERL was associated with longer PFS versus PBO + ERL [aEGFR+: median PFS (mPFS) = 15.2 versus 11.1 months, HR = 0.63, 95% CI 0.46-0.85; aEGFR-: mPFS = 22.1 versus 19.2 months, HR = 0.80, 95% CI 0.49-1.30].

Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease….EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC.

Eligible patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation...At the time of primary analysis, progression-free survival was significantly longer in the ramucirumab plus erlotinib group (19·4 months [95% CI 15·4-21·6])...Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC.

In the Phase 3 RELAY trial, ramucirumab/erlotinib demonstrated superior progression-free survival (PFS) over placebo/erlotinib in patients with EGFR-mutated metastatic NSCLC (median PFS 19.4 versus 12.4 months; HR =0.59, 95%CI =0.46-0.76; p < 0.0001)...Patients received oral erlotinib (150 mg daily) plus intravenous ramucirumab (10 mg/kg) or placebo Q2W until progressive disease or unacceptable toxicity... Overall patient compliance for LCSS and EQ-5D was >95%. TtD did not differ between treatment arms for LCSS Total Score (HR =0.962, 95%CI =0.690-1.343) and Average Symptom Burden Index (HR =1.012, 95%CI =0.732-1.400)...These data support the clinical benefit of ramucirumab/erlotinib in untreated EGFR-mutated metastatic NSCLC...

In all patients, RAM+ERL improved PFS. While ORR and DCR were comparable across all patients, DoR was superior with RAM+ERL. There were no clinically meaningful differences in the safety profiles between those with baseline TP53 mutation and wild-type....RAM+ERL is an efficacious first-line treatment option for patients with EGFR+ NSCLC, independent of TP53 status.

Pts with untreated metastatic EGFR+ NSCLC received oral ERL (150 mg/day) with either intravenous RAM (10 mg/kg) or placebo (P+ERL) every 2 weeks….In all pts, RAM+ERL improved PFS and DoR, while ORR (78% to 82%) and DCR (95% to 97%) were similar….The addition of RAM to ERL showed consistent benefit in both TP53wt and TP53mt EGFR+ NSCLC, suggesting that the RELAY regimen is a suitable first-line treatment option for pts with EGFR+ NSCLC irrespective of TP53 status.

Five of the six patients showed an objective systemic response. Although only one patient had a measurable CNS lesion at baseline, a confirmed intracranial partial response was observed....Ramucirumab in combination with erlotinib or osimertinib showed safety for EGFR-mutated NSCLC with brain metastases.