Adjuvant Erlotinib Does Not Improve OS Over Observation in Resected EGFR-Mutant NSCLC

June 8, 2026 | Kyle Doherty

Key Takeaways From the Phase 3 Alliance A081105 Trial

• The median OS was 9.7 years (95% CI, 8.4-not evaluable [NE]) with erlotinib (n = 182) vs 9.2 years (95% CI, 7.7-NE) with placebo or observation (n = 182; HR, 0.86; 95% CI, 0.58-1.28; 1-sided P = .232).
• The median DFS values were 5.6 years (95% CI, 4.2-6.9) and 4.1 years (95% CI, 3.2-6.1), respectively (HR, 0.75; 95% CI, 0.55-1.02; 1-sided P = .034).
• Grade 3 AEs occurred in 39.3% of erlotinib-treated patients vs 23.1% of placebo-treated patients.

Adjuvant erlotinib (Tarceva) did not significantly improve overall survival (OS) compared with placebo or observation in patients with completely resected stage IB through IIIA EGFR-mutant non–small cell lung cancer (NSCLC), according to the final OS analysis of the phase 3 Alliance A081105 trial (NCT02193282) presented at the 2026 ASCO Annual Meeting.¹

Findings from the study revealed that the median OS was 9.7 years (95% CI, 8.4-not evaluable [NE]) with erlotinib (n = 182) vs 9.2 years (95% CI, 7.7-NE) with placebo or observation (n = 182; HR, 0.86; 95% CI, 0.58-1.28; 1-sided P = .232). The median disease-free survival (DFS) values were 5.6 years (95% CI, 4.2-6.9) and 4.1 years (95% CI, 3.2-6.1), respectively (HR, 0.75; 95% CI, 0.55-1.02; 1-sided P = .034).

“Post operative erlotinib did not improve OS in patients with stage IB to IIIA EGFR-mutated NSCLC,” Ramaswamy Govindan, MD, the Anheuser Busch Endowed Chair in Medical Oncology, a professor of medicine in the Division of Oncology, and the director of the Section of Medical Oncology at Washington University Medicine in Saint Louis, Missouri, stated during the presentation. “However, in the same population it improved the DFS modestly, yet osimertinib [Tagrisso] remains the standard [of care] in this setting.”

How was Alliance A081105 designed?

Alliance A081105 was an randomized that enrolled patients with completely resected stage IB (≥ 4 cm), II, or IIIA nonsquamous NSCLC with EGFR exon 19 deletions or L858R mutations.1,2 Eligible patients were also required to have negative surgical margins, an ECOG performance status of 0 to 1, and standard postoperative therapy (if applicable).1

Patients were randomly assigned 1:1 to erlotinib 150 mg orally once daily for up to 2 years or placebo (later observation, following a protocol amendment). Stratification factors included stage (IB ≥ 4 cm vs II vs IIIA), prior chemotherapy (yes vs no), exon 19 deletion status (yes vs no), and ECOG performance status (0 vs 1).

The primary end point was OS. DFS and safety represented secondary end points. The baseline characteristics were generally well balanced between the 2 arms; the median age was 66.0 years (IQR, 59.0-74.0) in the erlotinib arm (n = 191) and 68.0 years (IQR, 61.0-72.0) in the placebo/observation arm (n = 188). Most patients in both arms were White (67.5% vs 72.3%), female (70.2% vs 69.1%), had disease harboring EGFR exon 19 deletions (53.9% vs 54.8%), and underwent lobectomy and greater (92.7% vs 90.4%). Most patients in both arms also had stage II disease (50.8% vs 51.1%), underwent prior chemotherapy (83.2% vs 81.4%), and had an ECOG performance status of 0 (61.3% vs 58.5%).

What were the additional efficacy results?

The 2-year OS rates in the erlotinib and placebo/observation arms were 95.4% (95% CI, 90.9%-97.6%) and 94.4% (95% CI, 89.9%-96.9%), respectively; the respective 5-year OS rates were 78.6% (95% CI, 71.6%-84.1%) and 78.0% (95% CI, 70.9%-83.6%), respectively. The 2-year DFS rates were 77.2% (95% CI, 69.8%-83.0%) and 64.3% (95% CI, 56.4%-71.1%) respectively, and the 5-year DFS rates were 56.0% (95% CI, 47.4%-63.7%) and 48.4% (95% CI, 40.3%-56.0%), respectively.

What were the notable safety data?

The median percentages of total doses received in the investigational and control arms were 46.1% (IQR, 5.4%-70.2%) and 31.3% (IQR, 9.1%-49.9%), respectively. Patients came off treatment due to completion per protocol (37.2% vs 91.0%), adverse effects (AEs)/complications (24.1% vs 1.6%), patient withdrawal/prior refusal/after beginning protocol therapy (18.8% vs 2.6%), disease progression, relapse during active treatment, or other complicating disease (6.8% vs 4.8%), alternative therapy (6.3% vs 0.0%), death on study (1.0% vs 0.0%), and other reasons (5.8% vs 0.0%).

Grade 3 AEs occurred in 39.3% of erlotinib-treated patients vs 23.1% of placebo-treated patients. The most commonly reported grade 3 or higher AEs in the erlotinib arm were diarrhea (7.7%), acneiform rash (7.7%), and maculopapular rash (6.0%). Three patients in the erlotinib arm experienced grade 5 AEs.
“We have [also] done a whole genome, whole-exome transcriptome sequencing of all samples… I’m hoping that we will learn prognostic and predictive markers from this group,” Govindan said during his conclusion. “We are also doing genomic analyses from the screening trial; the work is nearly complete and hopefully we will get those data out fairly soon.”

Disclosures: Govindan had no relevant financial relationships to disclose.

References

1. Govindan R, Mandrekar SJ, Kozono DE, et al. Adjuvant erlotinib versus observation after complete resection of EGFR-mutant NSCLC: final overall survival results of Alliance A081105. J Clin Oncol. 2026;44(suppl 16):8001. doi:10.1200/JCO.2026.44.16_suppl.8001
2. Erlotinib hydrochloride in treating patients with stage IB-IIIA non-small cell lung cancer that has been completely removed by surgery (an ALCHEMIST treatment trial). ClinicalTrials.gov. Updated May 29, 2026. Accessed June 8, 2026. https://clinicaltrials.gov/study/NCT02193282