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M. Brada
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-003 - TAX-TORC: The Novel Combination of Weekly Paclitaxel and the Dual mTORC1/2 Inhibitor AZD2014 for the Treatment of Squamous NSCLC (ID 4803)
14:30 - 14:30 | Author(s): M. Brada
- Abstract
Background:
The dual mTORC1/2 inhibitor AZD2014 has multiple effects on cell growth, apoptosis, angiogenesis and metabolism in cancer cells. AZD2014 increases the efficacy of paclitaxel in preclinical models, including patient derived xenografts. These data and clinical responses in the dose escalation arm of the TAX-TORC study led to an expansion cohort of 40 patients with squamous non-small cell lung cancer (sqNSCLC).
Methods:
Patients, of ECOG performance status 0-1, with sqNSCLC who had received at least one line of platinum-based chemotherapy were eligible for the study. Paclitaxel was dosed once weekly at 80mg/m[2], 6 weeks out of 7. AZD2014 was dosed BD, 3 days per week starting with the paclitaxel dosing. The cohort was started at 50mg AZD2014 BD.
Results:
Thirty-two patients have been treated, 24 male/8 female with median age 68 years. The median number of previous treatments was 1 with 6/32 (19%) having received a prior taxane (docetaxel or paclitaxel). Analysis of data from the first 17 patients, by the safety review committee, showed that fatigue, skin rash and diarrhoea were the most common toxicities in 59%, 47% and 41% patients respectively. The majority of toxicities were CTCAE grades 1 or 2 (112/123, 91%) and reversible with AZD2014 interruption or reduction. However, there were 9 grade 3 and 4 toxicities and 2 incidences of grade 5 respiratory infection. There were 2/17 (12%) responses though patients often stopped early due to toxicity. Following the safety review, the dose of AZD2014 was reduced to 25mg BD which is a pharmacodynamically active dose associated with fewer toxicities. Fifteen additional patients have subsequently been treated at this lower dose. Their most common toxicities were anaemia, alopecia and fatigue in 47%, 47% and 40% patients respectively. There have been no grade 5 events and only 8/78 (10%) grade 3 or 4 toxicities. The response rate in this cohort is 5/15 (33%) and recruitment is ongoing. Archival samples and circulating free DNA at baseline are being assessed with targeted next generation sequencing to explore putative predictive biomarkers for response and resistance.
Conclusion:
We have established a tolerable dose and schedule for the combination of weekly paclitaxel and AZD2014. The promising response rate of 33% in previously treated sqNCSLC patients warrants further investigation. The study is supported by AstraZeneca, Cancer Research UK, Experimental Cancer Medicine Centre and NIHR Biomedical Research Centre Initiatives.
