1097P - Impact of tumor and liquid rebiopsy in metastatic non-small cell lung cancer with EGFR/ALK/ROS oncogenic drivers, progressing after optimal target therapy

Background

For metastatic NSCLC (mNSCLC) patients (pts) with oncogenic driver (EGFR mutation or ALK/ROS translocation), progressing after tyrosine kinase inhibitors (TKI), it is recommended to try to obtain a new mutational profile by associating liquid and tumor rebiopsy, according to local conditions and clinical modalities of progression. The objective of this study is to analyze the practices in terms of tissue and blood rebiopsies in mNSCLC EGFR/ALK/ROS pts progressing after TKI before their inclusion in a phase II trial (GFPC 06-2018) testing the effectiveness of immunotherapy-platin-based-chemotherapy combinations.

Methods

The analysis included 149 pts, 132 EGFR mutated, 13 ALK and 5 and ROS translocated. We describe the rate of re biopsies according to oncogenic driver and previous TKI. No sampling was mandatory before inclusion in the study.

Results

The rate of liquid and or tissues rebiopsies whose 69/149 (46.3%): 48.4%, 30.8%, and 0% in EGFR mutated, ALK and ROS translocated pts respectively. Among the 64 EGFR-mutated pts, molecular biology was performed on tissue, blood or both in 39, 19 and 6 cases respectively. Previous target therapies were: one line of 3^rd generation (G)-TKI: 26 (41%) pts, one line of 1^st or 2^nd G-TKI: 12 (19%) pts, 1^st or 2^nd G-TKI followed by a 3^rd G-TKI: 18 (28%) pts, one line of 1^st G-TKI followed by 2^nd G-TKI: 3 (4%) pts. 47 (73%) pts still had their initial mutations; 9 (14%) pts had detectable T790M and 5 (8%) acquired C797S EGFR secondary mutation. Other mutations were found in 27 (42%) pts: TP53 (n=13), amplification of MET (n=4), STK11 (n=4), and PIK3CA (n=4), insertion exon 20 (n=3), KRAS (n=2), NRAS (n=2), CTNMB1 (n=2), APC (n=1), BRCA2 (n= 1) and RET (n=1). For the 5 ALK-translocated pts, one presented a G1202A resistance mutation.

Conclusions

In this population of patients progressing under optimal target therapy, and in sufficiently good general condition to be included in a chemotherapy trial, less than 50% of patients have liquid or tissue rebiopsy. For EGFR mutated patients, a resistance mechanism linked or not to EGFR is identified in respectively 32% and 48% of cases.

Clinical trial identification

NCT04042558.

Editorial acknowledgement

Legal entity responsible for the study

Groupe Francais de Pneumo-Cancérologie (GPFC).

Funding

Has not received any funding.

Disclosure

C. Ricordel: Financial Interests, Personal, Advisory Board: BMS, Takeda, AstraZeneca; Financial Interests, Personal, Funding: AstraZeneca. L. Bigay-Game: Financial Interests, Personal, Advisory Board: BMS, MSD, Takeda, AstraZeneca, Viatris, Ipsen, Amgen, Pfizer. M. Geier: Financial Interests, Institutional, Research Grant: BMS, Roche; Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, Pfizer, Sanofi, BMS, AstraZeneca. C. Decroisette: Financial Interests, Personal, Advisory Board: Sanofi, Janssen Cilag, AstraZeneca, Takeda, BMS, Sandoz, Novartis, Roche, Lilly, PFIZER. C. Daniel: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Novartis. F. Guisier: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, MSD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Takeda, Pfizer. A. Swalduz: Financial Interests, Personal, Advisory Board: Lilly, Roche. A.C. Toffart: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Amgen, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, MSD, Nutrician, Novartis, Pfizer. H. Doubre: Financial Interests, Personal, Advisory Board: BMS, Amgen, MSD, Roche; Financial Interests, Personal, Invited Speaker: Leo Pharma, Pfizer; Financial Interests, Personal, Other, Travel Congress: Novartis. J.M. Peloni: Financial Interests, Personal, Advisory Board: AstraZeneca. H. Morel: Financial Interests, Personal, Invited Speaker: Takeda. R. Veillon: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Roche; Financial Interests, Personal, Advisory Board: Janssens Cilag, Takeda; Financial Interests, Personal, Expert Testimony: AstraZeneca; Non-Financial Interests, Personal, Other, Travel Congress: Pfizer, Roche; Financial Interests, Institutional, Research Grant: Merck, Takeda, Novartis, GSK, AstraZeneca. C. Chouaid: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer, GSK, Roche, Sanofi, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Amgen. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. O. Bylicki: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Takeda, MSD; Financial Interests, Personal, Expert Testimony: ROCHE. All other authors have declared no conflicts of interest.