Report Finds Benefit With Third-Generation EGFR Inhibitor After Progression on Another Such Agent in Patients With Lung Cancer


Key Points

  • Osimertinib produced partial response in three of nine patients and stable disease in four patients with metastatic non–small cell lung cancer who had disease progression on rociletinib.
  • Central nervous system response was observed in patients with new brain metastases.

In a research letter in JAMA Oncology, Sequist et al reported clinical benefit with the recently approved third-generation EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor osimertinib (Tagrisso) in patients with metastatic non–small cell lung cancer who had disease progression during treatment with the investigational third-generation agent rociletinib.

Report Details

The report included all nine patients at Massachusetts General Hospital who had received rociletinib in a clinical trial and subsequently osimertinib in a separate clinical trial. Among the nine patients, T790M-positive status was documented in seven patients prior to rociletinib treatment and in eight patients prior to osimertinib treatment. Rociletinib was discontinued for progressive disease in all patients; six patients began osimertinib with no intervening therapy.

Rociletinib doses were 500 to 1,000 mg twice daily, with six patients requiring dose reduction. Osimertinib was given at 80 or 160 mg daily, with no dose reductions required. The best responses to rociletinib were partial response in two patients, stable disease in three patients, and progressive disease in four patients.


The best responses to subsequent osimertinib were partial response in three patients, stable disease in four patients, and progressive disease in two patients. Median progression-free survival was 208 days. Among the six patients who received osimertinib with no intervening therapy, three had partial response and three had stable disease for 207 to 375 days. Among the four patients with progressive disease as best response to rociletinib, including one of the previously mentioned patients, two had disease refractory to osimertinib and two had stable disease for 208 and 375 days. Central nervous system response to osimertinib was observed in three patients who developed new brain metastases on rociletinib.

The authors noted: “Further studies are needed to determine optimal sequencing of third-generation EGFR [tyrosine kinase inhibitors].”

The clinical trials of rociletinib and osimertinib were funded by Clovis Oncology and AstraZeneca, respectively. The research team was funded by LunGevity, Lungstrong, Targeting a Cure for Lung Cancer, Be a Piece of the Solution, and the National Cancer Institute.

Lecia V. Sequist, MD, MPH, of Massachusetts General Hospital Cancer Center, Boston, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.