Abstract 5243
Background
Randomized controlled trials are not feasible for rare cancer populations particularly when the investigational drug targets a molecular alteration shared by several tumor types with different natural histories. Innovative approaches that incorporate patients as their own control can be utilized in this setting. Growth Modulation Index (GMI) is the ratio of time to progression (TTP) with nth line of therapy (TTPn) to the most recent prior line of therapy (TTPn-1), and a GMI ≥1.33 has been proposed as a marker of meaningful clinical activity. We report here the GMI for patients (pts) diagnosed with TRK fusion cancer and treated with larotrectinib, a selective TRK inhibitor.
Methods
TRK fusion cancer pts enrolled in 3 clinical trials (NCT02122913, NCT02637687, NCT02576431) who have been on treatment for at least 6 months (or discontinued early) and had at least one prior line of systemic therapy in metastatic setting were eligible. GMI was calculated as a ratio of progression-free survival (PFS) with larotrectinib (PFSLaro) to TTP of the prior line of therapy (TTPn-1). PFS was determined by independent review committee (IRC) assessments using RECIST 1.1 criteria.
Results
As of a July 30, 2018 data cut, 53 pts (42 adults, 11 pediatric) were eligible. Sixteen pts (30.2%) had 2 prior therapies and 24 (45.3%) had ≥3 prior lines of therapy. Thirteen different tumor types were represented with the largest being soft tissue sarcoma (n = 12), lung cancer (n = 7), thyroid cancer (n = 6), and colon cancer (n = 6). The median GMI (IRC) was 2.87 (range: 0.01–48.75, Table). Thirty-five (66.0%) pts had a GMI ≥1.33. Five of 18 pts with a GMI <1.33 are still on treatment and non-progressive at the time of analysis.Table:
485P
GMI (PFSLarotrectinib/TTPprior_line) | IRC-assessed pts N = 53 |
---|---|
Mean (SD) | 6.00 (9.97) |
Median (min, max) | 2.87 (0.01, 48.75) |
GMI category, n (%) <1 ≥1 1 to 1.33 ≥1.33 ≥2 | 15 (28.3) 38 (71.7) 3 (5.7) 35 (66.0) 32 (60.4) |
Conclusions
TRK fusion cancer patients treated with larotrectinib had a clinically meaningful improvement in PFS compared to TTP on prior treatment as evidenced by a GMI >1.33 in two-thirds of evaluable patients.
Clinical trial identification
NCT02122913, NCT02637687, NCT02576431.
Editorial acknowledgement
Editorial assistance was provided by Michael Sheldon, PhD, of Scion, London, UK, funded by Bayer.
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
A. Italiano: Advisory / Consultancy: Bayer, Epizyme, ImmuneDesign, Lilly, Merck, MSD, Novartis, Roche; Research grant / Funding (institution): AstraZeneca, Bayer, Merck, MSD, Pharmamar, Roche. S. Nanda: Full / Part-time employment: Bayer. K. Keating: Full / Part-time employment: Bayer. B.H. Childs: Full / Part-time employment: Bayer. M. Fellous: Full / Part-time employment: Bayer. A. Drilon: Advisory / Consultancy: Loxo Oncology/Bayer, Ignyta, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Genentech/Roche, Takeda/Ariad/Millenium, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Bayer, Tyra; Research grant / Funding (self): Foundation Medicine; Licensing / Royalties: Wolters Kluwer; Honoraria (institution): Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho; Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: MORE Health. D.M. Hyman: Advisory / Consultancy: Chugai Pharma, CytomX Therapeutics, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer Pharmaceuticals, Genentech / F. Hoffmann-La Roche; Research grant / Funding (self): Loxo Oncology, Bayer Pharmaceuticals, PUMA Biotechnology, AstraZeneca.
Resources from the same session
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract
4325 - Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: insights of the MATCH-R study
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract