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R. Herbst
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MO16 - Prognostic and Predictive Biomarkers IV (ID 97)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:S. Toyooka, J.C. Yang
- Coordinates: 10/29/2013, 16:15 - 17:45, Parkside Auditorium, Level 1
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MO16.04 - Analysis of HER2 amplification in non-small cell lung cancers (NSCLCs) with acquired resistance (AR) to Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) (ID 2951)
16:30 - 16:35 | Author(s): R. Herbst
- Abstract
- Presentation
Background
Recent studies have demonstrated the feasibility of rebiopsy in patients (pts) with EGFR mutant NSCLC at the time of AR to the EGFR tyrosine kinase inhibitors (TKIs) erlotinib or gefitinib, and provide estimates of the prevalence of well described mechanisms of AR including the EGFR T790M mutation, MET amplification and small cell lung cancer (SCLC) transformation. HER2 amplification has also been described in cases of AR to EGFR TKIs, however, its exact frequency is still unclear. Moreover, comprehensive analysis of paired pre- and post-treatment samples to establish whether HER2 amplification is acquired during treatment with TKIs have not been performed. This prompted us to further investigate HER2 amplification in EGFR mutant NSCLC cases.Methods
Pts with metastatic or recurrent NSCLC who developed AR while on a molecularly targeted agent were enrolled on an IRB approved repeat biopsy protocol. Tumor biopsies were obtained at the time of AR, and histopathological and molecular analyses of the tumors were performed. Known mechanisms of AR to EGFR TKIs were analyzed (T790M mutation, MET amplification and SCLC transformation) as well as amplification of HER2. The presence of T790M was assessed either by Taqman or pyro-sequencing (unless T790M status was available from an outside institution). HER2 and MET amplification were determined using fluorescence in situ hybridization (FISH).Results
41 pts with AR to EGFR TKIs (erlotinib or gefitinib) were enrolled at YCC between Jan 2012 and May 2013. Histological analysis of all specimens revealed transformation of adenocarcinoma to SCLC in 3 cases (7%). Depending on the availability of tissue, samples were prioritized for T790M analysis followed by MET and HER2 amplification. T790M was identified in 36% of pts; MET and HER2 amplification were found in 11% and 10% of samples respectively. In the two cases with HER2 amplification, analysis of the pre-treatment specimen revealed that amplification of this receptor tyrosine kinase preceded treatment with EGFR-TKIs, however, the amplification level was lower pre-treatment in both cases. Specifically the ratio of HER2 to CEP17 probes was 2.8 pre-treatment in both cases and increased to 4.3 and 8 following TKI treatment. HER2 amplification was mutually exclusive with the other tested mechanisms of resistance.Conclusion
T790M was the most commonly identified mechanism of AR to EGFR TKIs in the YCC cohort consistent with other studies. MET amplification, HER2 amplification and SCLC transformation were also observed. The observation that HER2 was amplified pre-treatment warrants further investigation of HER2 amplification in AR and pre-treatment specimens. Whole exome sequencing of specimens without known resistance mechanisms is ongoing.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO18 - NSCLC - Targeted Therapies IV (ID 116)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:L. Horn, J. Wolf
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Auditorium B, Level 1
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MO18.06 - BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 1949)
16:45 - 16:50 | Author(s): R. Herbst
- Abstract
- Presentation
Background
Effective therapeutic strategies for mutant KRAS and other biomarkers of resistance in refractory NSCLC remain an unmet medical need, while a personalized medicine approach is increasingly adopted in NSCLC guided by tumor molecular profiling. The BATTLE-2 clinical study is using EGFR, PI3K/AKT and MEK inhibitors and is designed to identify biomarkers for optimal patient selection for these therapies (ClinicalTrials.gov NCT01248247).Methods
This is a four-arm, open-label, multi-center, biopsy-driven, adaptive randomization, phase II clinical trial in NSCLC pts that failed at least 1 prior line of therapy. Patients are adaptively randomized to 4 arms: erlotinib, erlotinib plus the AKT inhibitor MK-2206, MK-2206 plus the MEK inhibitor selumetinib, and sorafenib. The primary objective is 8-week disease control rate (DCR). The trial is conducted in 2 stages. In Stage 1, 200 evaluable pts are adaptively randomized (AR) based on observed 8-week DCR and KRAS mutation status while predictive biomarkers are being developed by means of gene expression profiling, targeted next generation sequencing and protein expression. EGFR sensitizing mutations and EML4/ALK translocation in pts that are erlotinib and crizotinib naïve are exclusion criteria, while erlotinib resistant patients are excluded from erlotinib monotherapy. In Stage 2, the AR model is refined to include the most predictive biomarkers tested in Stage 1, with subsequent Stage 2 AR based on the new algorithm, to a total of 400 evaluable pts. Selection of Stage 2 single and/or composite markers follows a rigorous, internally and externally reviewed statistical analysis that follows a training, testing methodology with validation in stage 2 of the trial. All Stage 1 and 2 randomization biomarker assays are CLIA-certified.Results
286 pts have been enrolled, 236 biopsies performed,172 pts randomized, and 167 pts treated. 144 pts are evaluable for the 8-week DCR endpoint. Within the randomized pts group KRAS mutation rate is 22.8%, and EGFR mutation rate 14.8%, while 36.3% patients have been previously treated with erlotinib. Treatment is well tolerated with no unanticipated toxicity.Conclusion
Accrual updates, demographics, and further details will be presented at the meeting. (Supported by NCI R01CA155196-01A1)Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS13 - Statistics of Personalised Medicine (ID 30)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Statistics
- Presentations: 1
- Moderators:M. Redman, J. Crowley
- Coordinates: 10/29/2013, 14:00 - 15:30, Parkside 110 A+B, Level 1
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MS13.2 - Clinical Trial Designs for Biomarker Driven Therapies in Advanced Disease (ID 517)
14:25 - 14:45 | Author(s): R. Herbst
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS19 - New Health Technology for Lung Cancer; Assessment and Implementation (ID 36)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:Y. Lievens, F.(. Kong
- Coordinates: 10/30/2013, 14:00 - 15:30, Parkside Ballroom B, Level 1
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MS19.2 - Cost Effectiveness of Prevention of Lung Cancer (Developed and Developing World) (ID 547)
14:25 - 14:45 | Author(s): R. Herbst
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P3.23 - Poster Session 3 - Tobacco Control, Prevention and Chemoprevention (ID 164)
- Event: WCLC 2013
- Type: Poster Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.23-004 - Thoracic oncology providers and addressing tobacco use in cancer patients: a report from an IASLC survey. (ID 2047)
09:30 - 09:30 | Author(s): R. Herbst
- Abstract
Background
Background: Tobacco use increases toxicity, recurrence, second primary cancers, and mortality in cancer patients. However, oncologists do not routinely provide assistance with tobacco cessation and little is known about potential barriers that could be addressed to improve cessation practices among oncologists.Methods
Methods: An online survey was sent to IASLC members querying demographics, tobacco assessment and cessation practices, perceptions of tobacco use by cancer patients, and barriers to tobacco cessation intervention. Results are reported and multivariate analyses were performed to identify likely barriers to tobacco assessment and cessation.Results
Results: A total of 1,507 IASLC members responded to the survey representing a 40.5% response rate. Most respondents reported that tobacco use affected cancer outcome (92%) and that tobacco cessation should be a standard part of cancer care (90%). However, whereas 90% indicated that they regularly asked about tobacco use, only about 40% regularly discussed medications or provided cessation assistance. A lower likelihood of assessing tobacco use was associated with the following demographic variables: a) location outside of the United States (USA), b) practice non-academic centers, c) fewer years of service as a medical provider, d) less time spent on clinical activities, or e) current smoking. Variables associated with a decreased likelihood of giving advice to stop smoking were a) location outside of the USA and b) less time spent in clinic. A lower likelihood of providing cessation assistance was associated with providers outside of the USA. After adjustment for demographic variables, variables associated with increased likelihood of assessing tobacco use were a) providers who felt cessation affected outcome and b) providers who reported more training on cessation is needed. An increased likelihood to advise patients to stop smoking was observed in respondents who reported that additional cessation training is needed whereas a lack of time was reported as a variable that decreased likelihood to provide patient advice. Variables associated with a decreased likelihood to provide tobacco cessation assistance included: a) lack of time, b) lack of training, c) lack of available resources, and d) perception that tobacco cessation was a waste of time. However, variables associated with an increased likelihood to discuss medications or provide cessation assistance included respondents who a) reported having had adequate training in tobacco cessation or b) who reported that additional training is needed for clinicians.Conclusion
Conclusions: Most IASLC member oncologists who responded to the survey asked about tobacco use, but few routinely provided tobacco cessation assistance to their patients. Cancer patients need increased access to tobacco cessation support. Differences in the measurements of perceived barriers suggest that efforts are needed to increase cessation resources and clinician education in order to improve tobacco cessation support for cancer patients.
