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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
EGFR-mutated lung cancer is driven by a single faulty growth receptor and is treated first with a pill rather than chemotherapy. Osimertinib keeps the disease under control for about a year and a half on average, adding chemotherapy or the antibody amivantamab extends that further, and three years of osimertinib after surgery roughly halves the risk of death in early-stage disease.
EGFR mutations were discovered in 2004 when three Boston groups worked out why a minority of lung cancers, mostly in never-smoking women and East Asian patients, melted away on gefitinib. The IPASS trial (2009) then showed that in mutation carriers gefitinib beat chemotherapy and in non-carriers it was worse, which made EGFR testing mandatory before first-line treatment and established the model of a driver mutation matched to a pill. Exon 19 deletions and L858R are the classical sensitising mutations; exon 20 insertions are resistant to the classical inhibitors; and uncommon mutations (G719X, L861Q, S768I) respond best to afatinib or osimertinib.
Osimertinib, designed against the T790M resistance mutation, beat gefitinib and erlotinib first line in FLAURA (2018): median progression-free survival 18.9 versus 10.2 months and overall survival 38.6 versus 31.8 months, with far less brain progression. Two trials then built on it: FLAURA2 (2023) added platinum-pemetrexed to osimertinib (progression-free survival 25.5 versus 16.7 months, hazard ratio 0.62, with the 2025 survival analysis also in favour), and MARIPOSA (2024) combined the EGFR-MET bispecific antibody amivantamab with lazertinib (23.7 versus 16.6 months, hazard ratio 0.70, and longer overall survival), at the cost of rash, nail changes and venous thrombosis. For exon 20 insertions, PAPILLON (2023) showed amivantamab plus chemotherapy beat chemotherapy (11.4 versus 6.7 months, hazard ratio 0.40) and sunvozertinib was approved in 2025 after platinum chemotherapy. After osimertinib the escape routes are MET amplification (osimertinib plus savolitinib), C797S, small-cell transformation and, most often, no identifiable mechanism, where amivantamab plus chemotherapy (MARIPOSA-2) and the TROP2 antibody-drug conjugate datopotamab deruxtecan are the options.
| Setting | Approach | Guideline |
|---|---|---|
| Advanced, first line (exon 19 deletion or L858R) | Osimertinib alone (FLAURA), osimertinib plus platinum-pemetrexed (FLAURA2) for patients with high burden or brain metastases who can take chemotherapy, or amivantamab plus lazertinib (MARIPOSA) with prophylaxis against rash and clots. | not mapped |
| Advanced, exon 20 insertion | Amivantamab plus carboplatin-pemetrexed first line (PAPILLON); sunvozertinib after platinum chemotherapy. | not mapped |
| Advanced, after osimertinib | Biopsy or plasma test for the mechanism: osimertinib plus savolitinib for MET amplification; otherwise amivantamab plus platinum chemotherapy (MARIPOSA-2), platinum-pemetrexed, or datopotamab deruxtecan after chemotherapy; platinum-etoposide for small-cell transformation. | not mapped |
| Resected stage IB to IIIA | Surgery, adjuvant platinum chemotherapy where indicated, then three years of osimertinib (ADAURA). | not mapped |
| Unresectable stage III | Concurrent platinum chemoradiation followed by osimertinib until progression (LAURA) rather than durvalumab. | not mapped |
| Brain and leptomeningeal metastases | Osimertinib has high brain penetration and is preferred; stereotactic radiosurgery for symptomatic or large lesions; high-dose osimertinib for leptomeningeal disease. | not mapped |