Osimertinib rechallenge after severe pneumonitis in Stage IV lung cancer

What happened, in summary

A 57-year-old woman with a 12 pack-year smoking history was diagnosed in September 2013 with Stage IV lung adenocarcinoma carrying an EGFR exon 19 deletion. She presented with a malignant pleural effusion and began erlotinib the following month, maintaining an excellent response for 4 years.

By November 2017, PET imaging showed new liver and bone metastases. Testing identified an acquired EGFR T790M mutation, and she switched to osimertinib in December. Within 3 weeks she developed severe shortness of breath and acute hypoxic respiratory failure requiring intensive care. Osimertinib was stopped, and she received methylprednisolone 60 mg every 6 hours for 5 days followed by a 2-month prednisone taper. Within 1 month she no longer needed supplemental oxygen.

She then completed 4 cycles of carboplatin and pemetrexed followed by maintenance pemetrexed, but her liver disease progressed after 3 months. In May 2018 she chose to retry osimertinib, starting at 80 mg every other day with prednisone. Over the next 3 months, prednisone was tapered and osimertinib increased to 80 mg daily. She achieved a significant tumour response without recurrent pneumonitis.

After 11 months on the rechallenge, she developed progressive leptomeningeal carcinomatosis in April 2019, marking another setback in her metastatic cancer course.