Abstract B41: Different clinical outcomes of systemic chemotherapy in non-small cell lung cancer without EGFR and K-ras mutation according to smoking status.
Authors: Hong Sook Hee , Kang JinHyoung , Jeon Eun kyung , Kim Seung Joon , Lee Kyo-Young , Roh Sang young 
Published: August 2014

Background: The current treatment strategy in non-small cell lung cancer (NSCLC) adenocarcinoma without epidermal growth factor receptor (EGFR) activating mutation or anaplastic large cell kinase gene (ALK) rearrangement does not differentiate between genotype or smoking status even though resent advances in molecular study in NSCLC. In terms of second line treatment, pemetrexed is considered as a standard treatment in non-squamous NSCLC without EGFR activating mutation or ALK rearrangement. We retrospectively analyzed clinical outcomes of systemic chemotherapy according to molecular characteristics.

Methods: Between 2006 and 2012, 131 patients with stage 4 NSCLC adenocarcinoma patients who were enrolled in a Seoul St. Mary's hospital lung cancer multidisciplinary center registry were available for molecular pathology regarding EGFR and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing.

Results: Among 131 patients, the frequency of EGFR mutations, KRAS mutations, and no mutations in both genes (double negative [DN]) was 28.2%, 5.3% and 66.4% respectively. Among the DN genotype, 47.1%were never smoker and 37.9% were female. The median progression free survival (PFS) with 1st line platinum based combination chemotherapy was 5.4 months (95% CI: 3.7-7.02) for DN genotype and 7.4 months (95% CI: 5.73-9.06) for EGFR mutation group (p=0.047). According to smoking status, the median PFS with 1st line platinum based combination chemotherapy for never smokers in EGFR mutation group was significantly longer than the DN group (DN-N) (8.4 vs 6.7 months: p=0.018). However among the smokers, no significant difference in median PFS with 1st line chemotherapy between EGFR mutation and DN group (DN-S) were found (6.7 vs 4.6 months: p=0.515). In terms of second line treatment except EGFR tyrosine kinase inhibitors (EGFR-TKI), 64% of DN group and 70.3% of EGFR mutation group received pemetrexed, 21% of DN group and 29.7% of EGFR mutation group received docetaxel. 15.1% of DN group received EGFR-TKIs. The median PFS with second line treatment in DN-N group was 7.7 months (95% CI: 2.1-18.9), 3.1 months (95% CI: 1.4-4.8) and 4.4 months (95% CI: 2.2-6.5) for pemetrexed, docetaxel and EGFR-TKI respectively (p=0.009). However, no significant differences in median PFS between second line treatments was found in DN-S group [3.0 vs 2.8 vs 1.7 months for pemetrexed, docetaxel and EGFR-TKI respectively (p=0.100)]. In EGFR mutation group, no significant difference between pemetrexed and docetaxel was found according to the smoking status.

Conclusions: NSCLC without EGFR and K-ras mutation (DN group) had different clinical outcomes according to smoking history. Smoking history could be a useful clinical marker to choose a second-line treatment. However, further genomic study to find a druggable target in this group should be conducted.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B41.

Citation Format: Sook Hee Hong, JinHyoung Kang, Eun kyung Jeon, Seung Joon Kim, Kyo-Young Lee, Sang young Roh. Different clinical outcomes of systemic chemotherapy in non-small cell lung cancer without EGFR and K-ras mutation according to smoking status. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B41.