# COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib

Source: https://onco.cc/key-papers/paper-nct04765059-esmo-open-2025/  
OnCo record `paper-nct04765059-esmo-open-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the COMPEL trial registered as NCT04765059, in ESMO Open (2025), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: COMPEL (NCT04765059) was a global, randomized, double-blind study that evaluated osimertinib plus chemotherapy versus placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) following non-central nervous system (CNS) progression on first-line osimertinib.

Patients and methods: Patients were randomly assigned to receive osimertinib 80 mg, or placebo, once daily (o.d.) in combination with chemotherapy [cisplatin 75 mg/m 2 or carboplatin area under the curve 5 plus pemetrexed 500 mg/m 2 every 3 weeks (q3w) for four cycles], followed by osimertinib 80 mg, or placebo, o.d. in combination with maintenance pemetrexed (500 mg/m 2 q3w) until progression. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included CNS PFS according to CNS metastases status at baseline and overall survival (OS).

Results: Ninety-eight patients were randomly assigned (49 per arm). Median PFS in all patients was 8.4 months [95% confidence interval (CI) 5.7-11.8 months] with osimertinib plus chemotherapy versus 4.4 months (95% CI 3.5-5.6 months) with placebo plus chemotherapy [hazard ratio (HR) 0.43, 95% CI 0.27-0.70]. CNS PFS was longer with osimertinib plus chemotherapy versus placebo plus chemotherapy (HR 0.56, 95% CI 0.27-1.13) in patients without baseline CNS metastases (n = 75). Median OS in all patients was 15.9 months (95% CI 12.4-20.8 months) with osimertinib plus chemotherapy versus 9.8 months (95% CI 8.4-17.2 months) with placebo plus chemotherapy (HR 0.71, 95% CI 0.42-1.23). Grade ≥3 adverse events occurred more frequently with osimertinib plus chemotherapy (63%) than placebo plus chemotherapy (46%).

Conclusions: In patients with non-CNS progression on first-line osimertinib, osimertinib plus chemotherapy was associated with improved PFS and longer OS compared with placebo plus chemotherapy. These findings support osimertinib as a backbone treatment for EGFR-mutated advanced NSCLC through lines of therapy.

Indexed on Europe PMC as PubMed record 41139117 (DOI 10.1016/j.esmoop.2025.105807). Its abstract cites the registry id NCT04765059, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: ESMO Open
- Year: 2025
- DOI: 10.1016/j.esmoop.2025.105807
- Authors: Peled N, Tufman A, Sequist LV, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04765059 with the most citations, so it is the natural first reading for anyone following the COMPEL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- ESMO Open 2025: https://doi.org/10.1016/j.esmoop.2025.105807
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41139117/
- Europe PMC: https://europepmc.org/article/MED/41139117
- ClinicalTrials.gov NCT04765059: https://clinicaltrials.gov/study/NCT04765059

## Connected records

- trials: [A Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC)](https://onco.cc/trials/nct04765059/)
- journals: [ESMO Open](https://onco.cc/journals/esmo-open/)

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