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T. Vavala
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OA04 - Epidemiology and Prevention of Lung Cancer (ID 370)
- Event: WCLC 2016
- Type: Oral Session
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:L. Petruželka, S. Shastri
- Coordinates: 12/05/2016, 11:00 - 12:30, Schubert 4
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OA04.07 - Clinical Characteristics of Lung Adenocarcinoma in the Young: Results from the Genomics of Young Lung Cancer Study (ID 5578)
11:00 - 12:30 | Author(s): T. Vavala
- Abstract
- Presentation
Background:
Background: Lung cancer is increasingly recognized as a heterogeneous disease comprised of genomically defined subtypes with distinct targetable genomic alterations. However, it is unknown whether established lung cancer risk factors differ between these genomically distinct subtypes. In this study of the genomics of young lung cancer (GoYLC), we present preliminary results of lifestyle risk factors by specific genomic alteration to better characterize lung cancer in the young.
Methods:
Methods: Beginning in July of 2014, patients diagnosed with a bronchogenic lung cancer under the age of 40 were recruited to the GoYLC study. Informed consent was obtained in-person and virtually (online), allowing patients to participate globally, regardless of proximity to study sites (https://www.openmednet.org/site/alcmi-goyl). To date, this study has accrued a total of 101 cases, of which 85 are adenocarcinoma (AC). Stage 4 AC is the focus of this analysis.
Results:
Results: Among the 63 stage 4 AC cases, the most common genomic alterations were ALK rearrangements (n=28; 44% of stage 4 AC cases) and EGFR mutations (n=17; 27%) while the other genomic alterations (n=18; 29%) include ROS1, BRCA2, HER2, P53, RET and ATM. The prevalence of active smoking and/or exposure to passive smoking was highest among those with ALK (64%), intermediate for those with EGFR (47%) and lowest for those with other genomic alterations (39%). However, the prevalence of only active smoking was lowest among those with ALK (28%), followed by EGFR (35%) and highest for those with other genomic alterations (39%). The majority of patients with ALK rearrangements or EGFR mutations reported no family history of lung cancer (82% and 88%, respectively), compared with 67% among those with other genomic alterations.
Conclusion:
Conclusion: These preliminary results suggest that lifestyle characteristics and family history in young lung cancer patients may differ by genomic alteration. Passive smoke exposure was more prevalent among those with ALK rearrangements or EGFR mutations. Those with other genomic alterations, albeit, a heterogeneous group, were least likely to be exposed to passive smoking and more likely to be active smokers. We are continuing to enroll participants and are expanding the epidemiologic characterization to all study patients to evaluate if risk factors also differ by tumor stage and histology (Data to be presented). Importantly, this analysis lays the groundwork for the development of our more comprehensive epidemiology of young lung cancer study that may identify potential lifestyle and environmental risk factors related to specific genomic alterations.
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P3.06 - Poster Session with Presenters Present (ID 492)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Trial Design/Statistics
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.06-008 - Employing Remote Web Consenting and Social Media to Facilitate Enrollment to an International Trial on Young Lung Cancer (ID 4180)
14:30 - 15:45 | Author(s): T. Vavala
- Abstract
Background:
In 2014, the Addario Lung Cancer Medical Institute (ALCMI) launched a prospective study to characterize somatic and germline genomics of adolescents and young adult (AYA) patients under the hypothesis that lung cancer diagnosis at younger ages (<40) are more likely to have targetable genomic alterations. It is estimated that less than 2% of those newly diagnosed with lung cancer globally are AYA, thus presenting a striking recruitment challenge.
Methods:
The study workflow includes a dedicated website enabling e-consenting so patients can participate remotely from anywhere in the world, including the underserved, and employs social media to share our trial. We have an integrated data and bio repository that allows for seamless communication and completion of study activities including routing of blood and tumor specimens. ALCMI's "sister" foundation, the Bonnie J. Addario Lung Cancer Foundation, played a key role in educating patient and caregiver communities, including a social media campaign.
Results:
Accrual opened July 23, 2014. In the first 5 weeks of the study, 37 subjects consented versus the 5 projected. Of the 37 initially consented, 35 enrolled via the remote web-portal. As of June 15 2016, 104 subjects are enrolled (128 consented) in the study from 10 countries following a social media campaign of 89 discrete postings resulting in 21,062 active users out of 391,222 individual viewers and 675,680 impressions. Of the 104 subjects enrolled to date, 49% entered the study via the remote study portal with the balance recruited locally by participating ALCMI study sites. 45% of total accruals to date resulted from the education outreach by patient advocacy and patient to patient social networking.Figure 1
Conclusion:
This study clearly demonstrates the utility, speed and feasibility of remote, web-based screening and consenting platforms supported by patient-centric, advocate-driven social media efforts as novel approaches to "bringing research to the patient" for global clinical trials.
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SC10 - Squamous Cell NSCLC (ID 334)
- Event: WCLC 2016
- Type: Science Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:D.R. Gandara, M. Sebastian
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 3
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SC10.04 - Second-Line Therapy and Beyond in Squamous Cell NSCLC (ID 6640)
16:00 - 17:30 | Author(s): T. Vavala
- Abstract
- Presentation
Abstract:
Lung cancer is the leading cause of cancer-related mortality worldwide with 1.59 million deaths in 2012 and, with an estimated 1.8 million new lung cancer cases, it accounts for about 13% of total cancer diagnoses[1]. Non-small cell lung cancer (NSCLC) represents around 85% of all lung cancers with the majority of patients in advanced stages of the disease when diagnosed. Squamous cell carcinoma (SqCC) is the second most common histology in NSCLC accounting for 20-30% of cases[2]. Compared to the most frequent advanced lung adenocarcinoma, for which targeted therapies are available in case of presence of actionable mutations, treatment options for advanced lung SqCC have not changed with the same vividness in the last decade. But, to date, we can definitely say that also for these patients, the research has made progresses and new therapeutic scenarios are now open. Docetaxel and erlotinib were the only standard second-line treatment options for lung SqCC until, in December, 2014, the US Food and Drug Administration (FDA) approved ramucirumab (an anti-VEGFR-2 antibody) in combination with docetaxel, for the treatment of metastatic NSCLC patients who progressed during or after a platinum-based chemotherapy. In March 2015 nivolumab (an immune-checkpoint-inhibitor) was approved, for treatment of patients with metastatic SqCC, who progressed during or after a platinum-based chemotherapy and pembrolizumab (another immune-checkpoint-inhibitor) was approved in October, in the same setting of patients but whose tumors expressed PD-L1 (evaluated with the approved specific companion diagnostic, the PD-L1 IHC-22C3 pharmDx test). Finally, in April 2016, afatinib (an EGFR tyrosine-kinase inhibitor) was approved for treatment of patients with metastatic SqCC progressing after a platinum-based chemotherapy[3][,[4],[5],[6]]. It has been suggested that SqCC patients treated with docetaxel had a poorer survival compared to non-SqCC patients hypothesizing that docetaxel may be less effective in squamous compared with non-squamous lung cancer[7]. This was also evidenced in the phase III study (REVEL), in which squamous and non-squamous NSCLC patients were treated with docetaxel with or without ramucirumab: an OS benefit was seen with ramucirumab-docetaxel in the whole population (10.5 vs 9.1 months, HR 0.86, 95% CI 0.75–0.98, p = 0.023). In those patients who presented squamous cell histology (25%) the OS benefit, when treated with ramucirumab-docetaxel, was 9.5 months (4.4–17.6) vs 8.2 months (3.6–14.9, HR: 0.88, 95% CI 0.69–1.13) in placebo-docetaxel subgroup, while in those with non-squamous disease a better OS was described (11.1 months, Interquartile Range, IQR 5.3–24.3) in the ramucirumab-docetaxel group, vs 9.7 months (4.4–19.6) in the control group (HR 0.83, 95% CI 0.71–0.97), however it needs to be noted that subgroup analyses in this study were not pre-planned[4]. In LUX-Lung 8, a phase III study of second-line afatinib vs erlotinib, which enrolled squamous patients only, OS was 7.9 vs 6.8 months (HR 0.81, 95% CI 0.69–0.95, p = 0.007), in the afatinib subgroup vs erlotinib one[7]. Survival benefits highlighted in these studies when compared to older studies with docetaxel, while statistically significant, evidenced modest developments in the treatment of advanced-stage SqCC, as a consequence, novel therapeutic approaches have been considered and well accepted in the oncology community as well as largely awaited. Research on tumor immunosurveillance led to the development of PD-1 immune-checkpoint-inhibitors, such as nivolumab and pembrolizumab, and the PD-L1 inhibitors atezolizumab (MPDL3280A), durvalumab (MEDI4736) and avelumab (MSB0010718C)[8]. Nivolumab produced response rates equal to 15 to 17% with a median OS of 8.2 to 9.2 months, in phase I and II trials, among previously treated patients with advanced SqCC[5]. Then in the phase III CheckMate 017, Nivolumab induced a median OS of 9.2 months (95% CI, 7.3-13.3) vs 6 months (95% CI, 5.1-7.3) with docetaxel. The results in the docetaxel group were worst than expected. The risk of death was 41% lower with nivolumab than with docetaxel (HR, 0.59; 95% CI, 0.44-0.79; p < 0.001)[5]. PD-L1 expression is largely debated and its specific influence in the squamous population still needs further elucidations, since a total of 83% of the patients who underwent randomization (225 of 272 patients) in this trial had quantifiable PD-L1 expression and PD-L1 was assessed on archival tumor tissue, which may not have reflected its real status at the time of treatment[5]. SqCC is considered the tumor with the second highest amount of molecular aberrations, (eg, FGFR1 amplification, PIK3K3 abnormalities, DDR2 mutations), providing a plausible explanation about heterogeneity of treatment responses and efficacy results in the second-line setting[9]. However, despite the identification of those specific molecular alterations, progress in targeting oncogenic drivers in SqCC still runs behind adenocarcinoma. There is a need to develop predictive and specific molecular biomarkers, that might identify subgroups of patients with lung SqCC that are most likely to benefit from targeted treatments or immunotherapic approaches. In this context Pilotto et al. elaborated a project with the aim to evaluate the molecular profile of resected SqCC in order to identify those immunologic pathways and molecular aberrations potentially able to estimate the probability of disease recurrence (prognostic factors) and to characterize novel biomarkers, whose targeting with specific drugs could potentially limit the oncogenic potential and change the natural history of this disease (predictive factors). Preliminary results of this study were consistent with literature data: several molecular alterations might be identified [PIK3CA, MET, FGFR3, DDR2, FRS2, CDKN2A, SMAD4, PD-L1] and some of them might impact on the biological behavior of SqCC contributing in the determination of patients prognosis[10]. These data will be further presented at WCLC this year. In conclusion, as more treatment options turn out to be available for patients, it will become essential to tailor those choices on patient’s unique molecular characteristics and his own needs, identifying the best sequence of treatments, especially in the era of rising healthcare costs and longer lifespan of advanced lung cancer patients. References [1] WHO Statistics. http://www.who.int/mediacentre/factsheets/fs297/en/ [Accessed on 21 August , 2016]. [2] Travis WD. Pathology of lung cancer. Clin Chest Med 2011; 32: 669–92. [3] Garon EB et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014; 384: 665–73. [4] Brahmer J et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373(2):123-35. [5] FDA approves Keytruda for advanced non-small cell lung cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm465444.htm [Accessed on 21 August , 2016]. [6] Soria JC et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial Lancet Oncol 2015; 16: 897–907. [7] LE Ang Y et al. Profile of nivolumab in the treatment of metastatic squamous non-small-cell lung cancer. OncoTargets and Therapy 2016:9 3187–3195. [8] Melosky B et al. Pointed Progress in Second-Line Advanced Non–Small-Cell Lung Cancer: The Rapidly Evolving Field of Checkpoint Inhibition. J Clin Oncol 2016;34:1676-1688. [9] The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012; 489(7417): 519–525. [10] S. Pilotto et al. Analyzing prognostic outliers to unravel biologically and clinically relevant molecular and immunologic pathways: a model from resected squamous cell lung carcinoma (R-SQCLC). Poster presented at 58 Annual Meeting of the Italian Cancer Society helded in Verona on 5-8 September 2016.
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