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J.A. Stratmann
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-110 - ROS1 Translocation as a Bystander Mutation in T790M EGFR Mutated NSCLC (ID 4105)
14:30 - 14:30 | Author(s): J.A. Stratmann
- Abstract
Background:
Non small cell lung cancer comprises a number of subtypes that are defined by genetic alterations in terms of oncogenic driving mechanisms that constitute groundwork for the development of targeted therapy. EGFR mutations, as well as ROS1 translocations are two well described genetic alterations with prognostic and therapeutic implications and almost mutually exclusive occurance. Activating mutations in the EGF receptor gene are found in approximately 10% of european patients and large clinical trials with anti EGFR–kinase inhibitors set EGFR-TKIs as the gold standard of treatment. However treatment failure obligatory occurs within 8–13months and T790M gatekeeping mutation is found in approximately 60% as the resistance mechanism. 3rd generation TKI Osimertinib is a highly active treatment option in these patients. Furthermore ROS1 rearrangements are found in approximately 1-2% with various rearrangement partners. First clinical trials confirmed it´s pivotal role in NSCLC tumorigenesis as pharmacologic inhibition leads to tumor regression and durable response rates. We present a case report of a 74year old, ECOG 1 female patient, formerly smoker (15py), presenting with a relapsed, formerly stage II classified, metastatic L858R EGFR mutated adenocarcinoma, that progressed after 11months on Erlotinib therapy and harbored a T790M mutation as well as a bypassing ROS1 translocation. We initiated Osimertinib therapy and performed a short term radiologic evaluation after 4 weeks on the 3rd generation TKI.
Methods:
Tumor biopsies were obtained after clinical and radiologic findings of progressive disease and were analyzed by FISH for ROS1 and ALK (split fish technique), cMET (FISH) and EGFR (Therascreen EGFR-test by Qiagen). PET CT scans were performed before initiation of and 4 weeks after continuous Osimertinib therapy.
Results:
Molecular analysis revealed a T790M gatekeeping mutation, in addition a ROS1 (45% of vital tumor cells) translocation was detected. PET CT scans after Erlotinib failure confirmed metastatic and progressive disease with hypermetabolic and enlarged lymph nodes in the mediastinum and widespread tumor lesions juxtaposed to the pleural cavity at the right hemithorax with infiltration of the osseus thoracic wall. 4 weeks after initiation of Osimertinib therapy, repeated PET CT scans showed a partial remission of tumor burden with a concomitant complete resolution of pathologic glucose uptake.
Conclusion:
This is a rare case describing a tumor progress after acquired EGFR TKI resistance harboring a T790M mutation in addition to a ROS1 rearrangement. After one month of treatment with Osimertinib we found a metabolic CR indicating that ROS1 rearrangement had no clinical significance in this situation.
