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

J Roeper; M Netchaeva; A Lüers; S Schatz; M Falk; M Tiemann; N Neemann; LC Heukamp; C Wesseler; GH Wiest; S Sackmann; D Ukena; F Griesinger

doi:10.1055/s-0037-1619262

Pneumologie, Table of Contents

Pneumologie 2018; 72(S 01): S54-S55
DOI: 10.1055/s-0037-1619262

Sektion 11 – Pneumologische Onkologie

Posterbegehung – Titel: Lungenkarzinom II

Georg Thieme Verlag KG Stuttgart · New York

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

Authors

J Roeper

¹Universitätsklinik Innere Medizin – Onkologie, Pius Hospital, Carl von Ossietzky Universität Oldenburg
M Netchaeva

²Pius Hopital Oldenburg, Universität Oldenburg
A Lüers

²Pius Hopital Oldenburg, Universität Oldenburg
S Schatz

³Institut für Hämatopathologie Hamburg
M Falk

⁴Molekularpathologie, Hämatopathologie Hamburg
M Tiemann

³Institut für Hämatopathologie Hamburg
N Neemann

⁵Neo New Oncology Köln
LC Heukamp

⁵Neo New Oncology Köln
C Wesseler

⁶Lungenheilkunde (Pneumologie) im Thoraxzentrum, Asklepios Klinik Harburg
GH Wiest

⁷Asklepios Klinik Harburg
S Sackmann

⁸Klinik für Pneumologie und Beatmungsmedizin, Klinikum Bremen-Ost gGmbH
D Ukena

⁸Klinik für Pneumologie und Beatmungsmedizin, Klinikum Bremen-Ost gGmbH
F Griesinger

⁹Department of Hematology and Oncology, University Hospital, Pius-Hospital Oldenburg

Abstract

Full Text

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).

Tab. 1:

Clinical efficacy of atezo vs. doc in bTMB subgroups
	POPLAR study
	ITT (n = 287)		BEP (n = 211)
OS HR (95% CI)	0.73 (0.53, 0.99)		0.68 (0.50, 0.93)
PFS HR (95% CI)	0.94 (0.72, 1.23)		0.90 (0.68, 1.20)
bTMB subgroup	> 10	> 16		> 20
No. of patients	96	63		42
OSHR	0.59	0.56		0.51
PFS HR	0.68	0.57		0.58
	OAK study
	ITT (n = 850)		BEP (n = 583)
OS HR (95% CI)	0.73 (0.62, 0.87)		0.64 (0.53, 0.77)
PFS HR (95% CI)	0.95 (0.82, 1.10)		0.87 (0.73, 1.04)
bTMB subgroup	≥10	≥16		≥20
No. of patients	251	158		105
OS HR	0.69	0.64		0.65
PFS HR	0.73	0.65		0.61
BEP, biomarker-evaluable population; bTMB, tumor mutational burden in blood; ITT, intention to treat.

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.