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Attend this session at the
2019 ASCO Annual Meeting!


Session: Lung Cancer—Non-Small Cell Metastatic

Type: Poster Session

Time: Sunday June 2, 8:00 AM to 11:00 AM

Location: Hall A


Session: Lung Cancer—Non-Small Cell Metastatic

Type: Poster Discussion Session

Time: Sunday June 2, 4:30 PM to 6:00 PM

Location: Hall D1

Early circulating tumor (ct)DNA dynamics and efficacy of lorlatinib in patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC).

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
9019

Poster Board Number:
Poster Discussion Session (Board #342)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 9019)

Author(s): Alice Tsang Shaw, Jean-Francois Martini, Benjamin Besse, Todd Michael Bauer, Chia-Chi Lin, Ross A. Soo, Gregory J. Riely, Sai-Hong Ignatius Ou, Antonello Abbattista, Francesca Toffalorio, Holger C. Thurm, Miyako Satouchi, D. Ross Camidge, Steven Chuan-Hao Kao, Rita Chiari, Shirish M. Gadgeel, Enriqueta Felip, Benjamin J. Solomon; Massachusetts General Hospital, Boston, MA; Pfizer Inc, San Diego, CA; Gustave Roussy, Villejuif, France; Sarah Cannon Cancer Research Institute/Tennessee Oncology, PLLC, Nashville, TN; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; National University Cancer Institute, Singapore, Singapore; Memorial Sloan Kettering Cancer Center, New York, NY; Chao Family Comprehensive Cancer Center, University of California at Irvine Medical Center, Orange, CA; Pfizer Global Product Development-Oncology, Milan, Italy; Pfizer Global Product Development-Oncology, La Jolla, CA; Hyogo Cancer Center, Akashi, Japan; University of Colorado Cancer Center, Aurora, CO; Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia; Azienda Ospedaliera di Perugia, Perugia, Italy; University of Michigan/Rogel Cancer Center, Ann Arbor, MI; Vall d’Hebron Institute of Oncology, Barcelona, Spain; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Abstract Disclosures

Abstract:

Background: Lorlatinib is a selective, potent, brain-penetrant, 3rd generation (gen) ALK/ROS1 TKI approved for pts with advanced ALK+ NSCLC previously treated with a 2nd gen ALK TKI. We recently showed that ALK mutation tumor genotyping after failure of a 2nd gen ALK TKI may identify pts more likely to respond to lorlatinib.1 To identify other molecular response correlates, we evaluated if early ctDNA dynamics predict clinical outcome on lorlatinib. Methods: In pts enrolled on the ongoing ph 2 study (NCT01970865), plasma samples were prospectively collected for ctDNA analysis at baseline (BL), cycle 3 day 1 (C3D1, or 6 weeks) and end of treatment. Plasma DNA was analyzed using Guardant360. Change in variant allele fraction (dVAF)2 of ALK alterations (fusions and/or mutations) was calculated as (mean VAFC3D1) – (mean VAFBL); dVAF < 0 indicated decreased ctDNA at C3D1. BOR, PFS and OS were evaluated according to dVAF. Results: Of 121 paired BL/C3D1 samples collected from 158 ALK+ pts previously treated with one or more 2nd gen ALK TKIs, 57 (47%) harbored a detectable ALK alteration at BL. At C3D1, mean VAF of ALK fusions and/or mutations was significantly decreased compared to BL (-1.07, p = 0.0014). Mean tumor volume was reduced by 26% in pts with dVAF < 0 (n = 40), but only by 12% in pts with dVAF ≥0 (n = 13) (p = 0.049). Mean dVAF at C3D1 was significantly decreased compared to BL for pts with CR/PR, while there was no significant difference with SD or PD/IND; mean dVAF -1.84, -0.74, and +0.35 in pts with CR/PR, SD, or PD/IND, respectively (p = 0.0011, 0.1444 and 0.3383). Median PFS was 6.6 months (mo) in pts with dVAF < 0 (n = 44) and 2.6 mo in pts with dVAF ≥0 (n = 13) (HR = 2.6, 95% CI: 1.2, 5.8). Median OS was 18.0 mo in pts with dVAF < 0 (n = 34) and 8.6 mo in pts with dVAF ≥0 (n = 13) (HR 2.0, 95% CI, HR 0.9–4.6). Conclusions: Early ctDNA dynamics may predict lorlatinib efficacy in ALK+ NSCLC, with decreased ctDNA at 6 wks associated with better response and longer PFS. Further studies are needed to validate these findings and to determine whether early intervention based on dynamic ctDNA monitoring may improve outcome. References: 1. Shaw, et al. J Clin Oncol. 2019. 2. Raja, et al. Clin Cancer Res. 2018. Clinical trial information: NCT01970865

 
Other Abstracts in this Sub-Category:

 

1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

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