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Co-discovered EGFR mutations in lung cancer and has led the drug development that followed, from osimertinib to KRAS G12C inhibitors.
Pasi A. Jänne is Director of the Lowe Center for Thoracic Oncology and the Belfer Center for Applied Cancer Science at Dana-Farber Brigham Cancer Center. He is known for co-discovering in 2004 that EGFR mutations predict response to gefitinib in lung cancer, and for leading the drug development that followed, including FLAURA2 with osimertinib plus chemotherapy and the KRYSTAL-1 adagrasib lung study. His selected papers cover the activating EGFR mutations underlying gefitinib responsiveness, adagrasib in KRAS G12C-mutant lung cancer, and osimertinib with or without chemotherapy in EGFR-mutated lung cancer. He directs Dana-Farber's thoracic oncology centre and studies targeted therapy resistance.
| Title | Journal | Year |
|---|---|---|
| Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib | New England Journal of Medicine | 2004 |
| Adagrasib in non-small-cell lung cancer harboring a KRAS G12C mutation | New England Journal of Medicine | 2022 |
| Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC | New England Journal of Medicine | 2023 |
For a patient weighing the FLAURA2 regimen against osimertinib alone, the extra toxicity is front-loaded: the hardest months are the four induction cycles, and once pemetrexed stops the profile returns to that of osimertinib by itself. Kidney function deserves watching during pemetrexed maintenance.
Adding chemotherapy to osimertinib delays progression. Whether it extends life, and whether the same benefit could be had by giving the chemotherapy later to the patients who need it, is what the overall survival analysis and the registry watch on this roadmap are for.
It changed how resistance is investigated: the first question at progression on osimertinib is whether T790M is still there, because losing it means the tumour is no longer EGFR-driven in the growing compartment and another EGFR inhibitor will not help.
It made MET exon 14 a clinical entity rather than a sequencing curiosity, and identified the patients most likely to be missed: older people whose age would otherwise argue against broad sequencing.
It defined bypass resistance as a category and set the treatment rule that follows from it: keep blocking the original target and add an inhibitor of the bypass, which is the logic of every EGFR plus MET combination since.
Resistance to a targeted drug usually has a cause you can read off a sequence, which means it can be targeted in turn. Osimertinib exists because of this paper.
Why a drug can look useless in one trial and transformative in another: the trials had different proportions of the patients the drug was for. It is the argument for genotyping before drawing conclusions from a response rate.
Shares FLAURA2: long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced lung cancer, Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC, EGFR-mutated non-small-cell lung cancer, Non-small-cell lung cancer.
Shares FLAURA2: long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced lung cancer, FLAURA2, Osimertinib, Non-small-cell lung cancer.
Shares EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy, EGFR mutation and resistance of non-small-cell lung cancer to gefitinib, EGFR, Non-small-cell lung cancer.
Shares HER2-mutant non-small-cell lung cancer, EGFR-mutated non-small-cell lung cancer, EGFR, Non-small-cell lung cancer.
Shares HER2-mutant non-small-cell lung cancer, Osimertinib, EGFR, KRAS.
Shares HER2-mutant non-small-cell lung cancer, EGFR-mutated non-small-cell lung cancer, EGFR, Non-small-cell lung cancer.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS, Non-small-cell lung cancer.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS, Non-small-cell lung cancer.