Clinical Summary:

• Design/Population: The phase 3 REVOL858R trial randomized treatment-naive patients with advanced or recurrent EGFR L858R-mutated non-small cell lung cancer to receive either upfront osimertinib or a sequential strategy of erlotinib plus ramucirumab followed by osimertinib for acquired T790M disease.
• Key Outcomes: The sequential erlotinib plus ramucirumab strategy did not improve time to failure of strategy compared with upfront osimertinib. Overall survival, first and second progression-free survival, and response rates were generally similar between arms, while treatment discontinuation was more frequent with erlotinib plus ramucirumab.
• Clinical Relevance: These findings support upfront osimertinib as the preferred first-line strategy for EGFR L858R-mutated advanced non-small cell lung cancer, rather than reserving osimertinib for T790M-mediated progression after first-generation EGFR inhibition plus anti-angiogenic therapy.

Results from the phase 3 REVOL858R trial demonstrate that erlotinib plus ramucirumab followed by osimertinib did not improve outcomes compared with upfront osimertinib in patients with EGFR L858R-mutated advanced non-small cell lung cancer (NSCLC).

These results were presented by Naoki Haratake, MD, Kyushu Cancer Center, Fukuoka, Japan, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this trial, 232 treatment-naive patients with advanced or recurrent EGFR L858R-mutated NSCLC with an ECOG performance status of 0 or 1 were randomized 1:1 to receive either 80 mg of once daily osimertinib (n = 116) or 150 mg of once daily erlotinib plus 10 mg/kg of ramucirumab once every 2 weeks followed by osimertinib upon detection of acquired T790M mutations (n = 116). Patients enrolled in the erlotinib plus ramucirumab arm underwent mandatory tissue or liquid biopsy at progression. 

The primary end point was time to failure, defined as the time from randomization to disease progression or death during osimertinib treatment, or during primary treatment when osimertinib was not administered. Key secondary end points included overall survival (OS), objective response rate (ORR), time to first progression-free survival (PFS), time to second PFS, and safety. 

At analysis, median time to failure was 14.8 months in the osimertinib arm and 16.6 months in the erlotinib plus ramucirumab arm (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.78 to 1.38; P = .49). Median OS was 44 months in the osimertinib arm and 38.4 months in the erlotinib plus ramucirumab arm, with 3-year OS rates of 56.1% and 57.2%, respectively. ORR was 72.3% in the osimertinib arm and 66.3% in the erlotinib plus ramucirumab arm. Median time to first PFS was 14.8 months in the osimertinib arm and 14.9 months in the erlotinib plus ramucirumab arm, and median time to second PFS was 23.8 months and 25.1 months, respectively. Time to treatment failure was 12.6 months in the osimertinib arm and 11.2 months in the erlotinib plus ramucirumab arm. 

The most common adverse events were diarrhea and acneiform rash. Diarrhea occurred in 41% of patients receiving osimertinib and 54% of those receiving erlotinib plus ramucirumab, while acneiform rash occurred in 30% and 71%, respectively. Hypertension and proteinuria were reported in 39% and 18% of patients in the erlotinib plus ramucirumab arm. Interstitial lung disease occurred in 10% of patients receiving osimertinib and 2% of those receiving erlotinib plus ramucirumab. Adverse events leading to treatment discontinuation occurred in 21% and 36% of patients, respectively.

As Dr Haratake concluded, “A planned [erlotinib plus ramucirumab] to [osimertinib] strategy did not improve [time to failure of strategy] compared with upfront [osimertinib] in EGFR L858R-mutated NSCLC.” 

Source:

Haratake N, Hayashi H, Tsubouchi K, et al. Phase 3 clinical trial of the combination of erlotinib plus ramucirumab compared with osimertinib in untreated advanced or recurrent non-small cell lung cancer with EGFR L858R mutation: The REVOL858R trial (WJOG14420L). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA8518.