Impact on OS and PFS of 2nd and 3 rd Generation TKI in EGFR mt+ and ALK+ patients: Results of the NOWEL network

 

Introduction:

EGFR TKI treatment is standard of care in pts with metastasized NSCLC carrying an activating EGFR mutation. Targeted therapies achieve a higher ORR, OS, PFS and a better quality of life than chemotherapy in mt+ pts. With the advent of 2^nd and 3^rd generation TKI's effective in 1^st generation TKI resistant tumors, we wanted to study the impact of these drugs on the outcome of pts in a real life setting in 3 lung cancer centers.

Methods:

1477 pts from 3 cancer centers diagnosed with non-squamous cell NSCLC stage IV (UICC 7) were examined. Methods for the mutation testing were performed according to the German Oncopedia guidelines using either Sanger Sequencing, COBAS® or Next Generation Sequencing.

Results:

945/1477 (64%) pts with non-squamous cell NSCLC from 3 cancer centers were studied for the presence of tumor mutations, especially for EGFR and ALK mutations. The EGFR mutation rate was 16% (149/912), and the ALK-translocation rate 4% (26/700). Median OS in EGFR mt+ pts was 27 months (n = 149) compared to 11 months (n = 763) in pts with EGFR WT (p < 0.000). Median OS in EGFR mt+ pts depending on the center was 25 (n = 97) vs. 28 (n = 38) vs. 16 (n = 14) months respectively (center 1 vs. center 2 vs. center 3). Median OS in ALK+ pts was 24 months (n = 19) in center 1, 11 months (n = 5) in center 2 and in center 3 median OS was not reached (p < 0.025). The ORR in the CR/PR group was 54.2% for pts treated with chemotherapy and 77% for pts treated with TKI on 1^st line therapy. The chance to reach a CR/PR on 1^st line therapy is 2.83 higher for pts on TKI than for pts on chemotherapy (p < 0.02). The use of 3^rd gen TKI Osimertinib lead to a significantly higher OS (n = 20, median OS 67 months) than the use of only 1^st and 2^nd gen TKI (n = 122, median OS 23 months, p < 0.000). The hazard ratio HR for pts treated without Osimertinib was 4.66 [95% CI 2.006 – 10.81] (p < 0.000). Similarly, use of 2^nd and 3^rd gen ALKi impacted significantly on median OS: Crizotinib alone (n = 8), 15 months, Crizotinib followed by Ceritinib and/or Brigatinib/Alectinib (n = 14) median OS 25 months and 3 months for other therapies (n = 3) (p < 0.001).

Conclusion:

Small differences in OS were observed, depending on the treatment centers, but the use of multiple EGFR and ALK-I impacted highly significantly on the outcome of pts with EGFR mt and ALK-alterations in a real life setting.