Patients with metastatic non-small cell lung cancer and targetable molecular alterations in Germany. Treatment and first outcome data from the prospective German Registry Platform CRISP (AIO-TRK-0315)

Purpose: Guidelines for stage IV NSCLC recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) with targetable molecular alterations. Methods: Currently 163 sites in Germany have recruited > 4255 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. Progression-free survival (PFS) was determined in pts observed ≥ 1 year (recruited < 06/2017 (n = 906), outcome sample (ous)).

Results: 94%/65% of 1732/472 pts with non-squamous/squamous tumors were tested for any biomarker. In 2018 test rate was 96%/75% and 49%/33% were tested for all biomarkers (EGFR, ALK, ROS1, BRAF) with approved targeted therapies (aTT). An alteration in EGFR, ALK, ROS1 or BRAF was detected in 9%, 3%, 2%, and 2% of pts, respectively. Of pts with druggable EGFR mutation (EGFR+ pts, n = 149) 78% received EGFR-aTT in 1st-line. In 2nd-line, 20% received EGFR-aTT, 15% something else, 11% died prior to 2nd-line, 54% were still in 1st-line. Median PFS of EGFR+ pts was 7.1 months (n = 67, 61% events, 95%-CI 5.2 – 10.1), in total 46% (n = 31) of pts had died (ous). Of pts with druggable ALK alteration (n = 55), 47% received ALK-aTT in 1st-line. In 2nd-line, 22% received ALK-aTT, 11% something else, 13% died prior to 2nd-line, 54% were still in 1st-line. In the ous (n = 29), 55% (n = 16) of tumors had already progressed, in total 24% (n = 7) of pts had died. All 6 pts with druggable ROS1 alteration received chemotherapy, while 6 of the 9 pts with druggable BRAF mutation and start of treatment in 2017/18 received a BRAF-ATT in 1st-line. Conclusions: Pts are frequently tested for molecular alterations. While EGFR-aTT is well established as 1st-line and first data are promising for BRAF-aTT, pts with ALK/ROS alteration are not routinely treated with 1st-line aTT, reasons are not yet clear.

Disclosure Statement: None of the authors has declared a conflict of interest regarding the subject of this work.

Acknowledgements: CRISP supported by AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly Deutschland, MSD Sharp & Dohme, Novartis Pharma, Pfizer Pharma, Roche Pharma and Takeda Pharma Vertrieb.