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Lucinda Billingham
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-25 - TOURIST: Thoracic Umbrella Radiotherapy Study in Stage IV NSCLC: A Phase III Randomized Trial in Development (Now Available) (ID 1024)
10:15 - 18:15 | Author(s): Lucinda Billingham
- Abstract
Background
Non Small Cell Lung Cancer (NSCLC) is the leading cause of cancer mortality throughout the world with an incidence exceeding 1.2 million. 70% of NSCLC patients present with incurable disease with treatment aimed at alleviating symptoms, maintaining / improving quality of life as well as prolonging survival.
In the last decade there have been dramatic changes in systemic therapy (chemotherapy, immunotherapy, Tyrosine kinase Inhibitors (TKIs)). Despite these advances, many patients suffer from lororegional symptomatic relapse. This may benefit from local radiotherapy in addition to other standards of care such as symptom control. Radiotherapy remains widely used in the management of stage IV NSCLC but strategies vary hugely because the data originates from a series of dose fractionations trials in the 1990s when systemic therapy options were limited.
There is therefore limited evidence regarding the use and place of palliative radiotherapy in conjunction with modern systemic treatments and there is a need to assess benefits of advanced radiotherapy techniques in this population. The TOURIST trial aims to establish the utility of palliative thoracic radiotherapy in the primary treatment of stage IV NSCLC.
Method
This is a phase III platform that currently has 2 study arms, to cover the needs of differing patient populations, defined by the use of first line systemic therapy.
Study 1 (PRINCE) Patients receiving first line systemic therapy as standard of care, who have not progressed after 2-4 cycles are randomised 1:1 to either high dose palliative radiotherapy to the thorax, or to no radiotherapy while continuing on their standard systemic therapy. Co-primary endpoints: overall survival, PROMs recorded QOL, with progression free survival and time to next line of therapy, as secondary endpoints.
Study 2 (QUARTZ Lung) Asymptomatic patients unsuitable for standard systemic therapy randomised 1:1 to low dose palliative radiotherapy dose to the thorax or no radiotherapy. Telephone follow up will be used for PROMs data collection to measure QOL improvements.
Stratification factors for both studies will include bulk of thoracic disease, use of advanced radiotherapy techniques and performance status. The TOURIST trial intends to recruit 750 patients and is anticipated to open in 2020.
Result
Section not applicable
Conclusion
Section not applicable
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PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)
- Event: WCLC 2019
- Type: Plenary Session
- Track:
- Presentations: 1
- Moderators:Giorgio Vittorio Scagliotti, Ramon Rami-Porta
- Coordinates: 9/09/2019, 08:00 - 10:15, Barcelona (2005)
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PL02.09 - National Lung Matrix Trial (NLMT): First Results from an Umbrella Phase II Trial in Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2282)
08:00 - 10:15 | Author(s): Lucinda Billingham
- Abstract
Background
Oncogene-addicted NSCLC can achieve substantial clinical benefit with single-agent targeted therapy. Seeking to extend this paradigm to other more genetically complex NSCLC, we report first results of NLMT, an umbrella phase II trial whereby a bespoke next-generation sequencing screening panel (Stratified Medicine Programme 2) stratifies NSCLC patients to rationally selected targeted therapies. Uniquely we present results across the entirety of the platform to enable an assessment of the potential to further stratify medicine in advanced NSCLC. Novel methodology is used to ensure that the integrity of this ongoing platform trial is not jeopardised.
Method
NLMT uses a Bayesian adaptive design to screen currently 8 targeted drugs for signals of activity in 22 molecularly defined cohorts. For single agents, pre-specified clinically relevant outcomes are either median progression-free survival (mPFS) >3 months or objective response rate (ORR) and/or durable clinical benefit rate at 24 weeks (DCBR) >30%. Target recruitment for each cohort is 30 with futility analyses at 15. Recruitment continues in 19 cohorts. We report posterior probabilities (PP) of a clinically relevant outcome for closed cohorts and Bayesian predictive probability of success (PPoS) given observed data for open cohorts. This novel approach provides insight into the drug-biomarker combinations that have the strongest potential for further research.
Result
Over a 4 year period to end of March 2019, NLMT has recruited 286 patients from >4000 screened. Of 6 palbociclib cohorts (all proficient Rb): mPFS in KRAS mutation (n=30) is 5.8 months (PP>0.99); CDKN2A loss/non-squamous (n=27) passed its interim analysis; we predict >75% PPoS, given current data, in CDKN2A loss/squamous (n=16) and CCND1 amplification (n=13). Data for crizotinib show >90% PPoS in ROS1 gene fusions (n=8) and MET exon 14 skipping mutation (n=8), with less clear signal for MET amplification (n=9). Responses to selumetinib/docetaxel in NF1 mutation (n=16) warrant continuation. Recruitment to vistusertib was halted at interim for LKB1 single mutation (ORR=0/15, PP=0.003; DCBR=1/15, PP=0.026), but DCBR in LKB1/KRAS double mutation (n=23) warrant continuation. 4 cohorts receive capivasertib (n=22): data in PIK3CA amplifications (n=9) indicate <15% PPoS.
Conclusion
These first results from the largest stratified medicine dataset in NSCLC indicate further molecular stratifications could benefit from targeted therapies. Reporting interim outputs for all cohorts will allow reappraisal of the global stratified medicine strategy in cancer.
