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A. Ardizzoni
Moderator of
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ED 06 - Treatment of Elderly and High Risk Patients with Localized NSCLC (ID 6)
- Event: WCLC 2015
- Type: Education Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 4
- Moderators:A. Ardizzoni
- Coordinates: 9/08/2015, 14:15 - 15:45, 702+704+706
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ED06.01 - Medical Oncology (ID 1794)
14:20 - 14:40 | Author(s): A. Jatoi
- Abstract
- Presentation
Abstract:
In the United States, almost 50% of lung cancer patients are 70 years of age or older. Moreover, shifting demographics in the United States -- indeed, across the world -- suggest that oncologists will be seeing many more older patients with lung cancer in years to come. With cancer therapy, older patients often suffer higher and more severe rates of adverse events than their younger counterparts, yet many derive benefit from therapy. The challenges of treating older patients remain notable largely because enrollment in cancer clinical trials tends to show an underrepresentation of older patients. In this context, this talk with discuss 1) the ongoing challenges faced in treating older patients with lung cancer; 2) the relevant and instructive data derived to date from clinical trials; 3) the role of the comprehensive geriatric assessment; and 4) general recommendations on approaches to treating elderly lung cancer patients.
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ED06.02 - Radiation Therapy (ID 1795)
14:40 - 15:00 | Author(s): D. Ball
- Abstract
- Presentation
Abstract:
Non-small cell lung cancer is a disease of the elderly. In Australia in 2010, 84% of new lung cancers in men and 81% in women were diagnosed in people aged 60 years and older. The definition of “elderly” in the lung cancer radiotherapy literature varies with the lower limit ranging from 65 years (1) up to 85 (2). Older patients are not only more likely to develop toxicities of intensive treatment, but also to have less physiologic reserve to tolerate these toxicities. They include fatigue, pneumonitis, esophagitis and myelosuppression. Although older patients may have good performance status (ECOG 0-1), and be judged suitable for radical treatment, they may become deconditioned and harmed by treatment. Identification of these patients pre-treatment is challenging. An instrument to measure “frailty”, such as that devised by Fried et al (3) to predict post surgery complications would be useful in the radiotherapy setting. Frailty should be distinguished from performance status, which is only one measure of physiologic reserve; Fried’s frailty score includes measures of weight loss, grip strength and walking speed as well. Given the above, it is not surprising that older patients have worse survival than younger patients (4). Partly this may be due to a higher likelihood of suboptimal treatment (radiotherapy alone rather than concomitant chemoradiotherapy), and partly to the competing risks of non-neoplastic comorbidities. Once survival is adjusted for these effects, age is no longer associated with increased risk of death (4). It is generally agreed that functional rather than chronological age is a more important consideration in patient selection for radical treatment (2, 5). Age is certainly not a contraindication to treatment with SABR for stage I disease (6). The choice of chemotherapy to accompany radiotherapy in pateints with locally advanced disease is unclear because of a lack of trials performed specifically in a geriatric population. Carboplatin is usually preferred to cisplatin in patients over 70 because of its more favorable toxicity profile. The evidence for two drugs rather than one is limited. In a study of the Japan Clinical Oncology Group limited to patients 70 years and older, daily carboplatin added to 60 Gy of radiotherapy improved median survival from 16.9 to 22.4 months (p=0.02) compared with radiotherapy alone (7). Performance status, in the absence of a validated frailty score, remains a critical determinant of suitability for (chemo)radiotherapy. Patients with performance status ECOG 2 or worse seem not to benefit from treatment intensification, including when the intent of treatment is palliation (8). Comorbidity scores (Charlson, Colinet) appear to be closely linked to performance status, but there is insufficient evidence to support their use in clinical decision making. Diminished pulmonary function is sometimes thought to be a contraindication to radical radiotherapy - yet patients who are unfit for surgery, usually because of diminished cardiopulmonary reserve, are the very patients most likely to be referred for stereotactic ablative body radiotherapy (SABR). In fact, some studies suggest that patients developing symptomatic radiation induced lung injury were more likely to have a higher FEV1(9). However caution should be exercised in treating patients with pre-existing interstitial lung disease, including with SABR (10). Our approach is to judge a patient’s suitability for treatment based on their biological age. In older patients with locoregional disease and performance status ECOG 0-1 who are suitable for radical treatment, we would recommend full dose SABR for patients with peripheral stage I disease, and chemoradiation for locally advanced disease, 60 Gy with concomitant carboplatin and paclitaxel. Patients who are not fit for chemotherapy are treated with radiotherapy alone. If there is concern regarding the patient’s capacity to undergo a six week course, we either review the patient at 40 Gy , and if there is evidence of diminished tolerance, cease at that point. If there is concern that a patient will not tolerate a risk of grade 3 esophagitis, but the aim is improved local control rather than paliiation, we would offer a split course to allow for mucosal recovery (20 Gy in 5 fractions, followed by a 4 week break, then another 20 Gy). Although thought to be suboptimal because of the risk of repopulation, a split course schedule is less likely to produce high grade esophagitis than 36 Gy in 12 continuous fractions. For older patients with diminished performance status (ECOG 2 or greater) and for whom palliation is the objective, 20 Gy in five fractions is a reasonable option, and little more demanding on resources and patient inconvenience than a large single dose. References 1. Sigel K, Lurslurchachai L, Bonomi M, Mhango G, Bergamo C, Kale M, et al. Effectiveness of radiation therapy alone for elderly patients with unresected stage III non-small cell lung cancer. Lung Cancer. 2013;82(2):266-70. 2. Khor RC, Bressel M, Tedesco J, Tai KH, Ball DL, Duchesne GM, et al. Tolerability and outcomes of curative radiotherapy in patients aged 85 or more years. Med J Aust. 2015;202(3):153-5. 3. Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010;210(6):901-8. 4. Aridgides PD, Janik A, Bogart JA, Duffy S, Rosenbaum P, Gajra A. Radiotherapy for stage III non-small-cell lung carcinoma in the elderly (age >/= 70 years). Clin Lung Cancer. 2013;14(6):674-9. 5. Wanders R, Steevens J, Botterweck A, Dingemans A-MC, Reymen B, Baardwijk Av, et al. Treatment with curative intent of stage III non-small cell lung cancer patients of 75 years: A prospective population-based study. European Journal of Cancer. 2011;47(18):2691-7. 6. Palma D, Visser O, Lagerwaard FJ, Belderbos J, Slotman B, Senan S. Treatment of stage I NSCLC in elderly patients: a population-based matched-pair comparison of stereotactic radiotherapy versus surgery. Radiother Oncol. 2011;101(2):240-4. 7. Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, et al. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012;13(7):671-8. 8. Strom HH, Bremnes RM, Sundstrom SH, Helbekkmo N, Aasebo U. How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial. Clin Lung Cancer. 2015;16(3):183-92. 9. Kong FM, Wang S. Nondosimetric risk factors for radiation-induced lung toxicity. Semin Radiat Oncol. 2015;25(2):100-9. 10. Ueki N, Matsuo Y, Togashi Y, Kubo T, Shibuya K, Iizuka Y, et al. Impact of pretreatment interstitial lung disease on radiation pneumonitis and survival after stereotactic body radiation therapy for lung cancer. J Thorac Oncol. 2015;10(1):116-25.
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ED06.03 - Surgery (ID 1796)
15:00 - 15:20 | Author(s): M. Weyant
- Abstract
- Presentation
Abstract:
It is difficult to define what an elderly or truly “high risk” patient is in regards to offering surgical treatment of lung cancer. The World Health organization defines an elderly patient as being over age 65 although most practitioners of thoracic surgery would likely define an elderly patient as someone over age 70 (1) . Likewise the definition of a truly high-risk patient is difficult to determine. These patients are often described as having significant cardiopulmonary or other organ dysfunction that could be potentially worsened by the surgical event. In developed countries the average population age is increasing and the incidence of lung cancer is also increasing in elderly patients. Combined with the natural decline in lung and cardiac function these data suggests that there will likely be a steady and significant increase in elderly and high-risk patients who present for consideration of resection for localized lung cancer. Clinical data in the elderly and high-risk patients is hard to come by, as many of these patients are not represented in clinical trials despite the high proportion of these patients in the lung cancer population. The data that is available is often retrospective in nature but it suggests that treatment decisions in these patient groups should not solely be based on chronological age but should take into account the patient’s life expectancy, quality of life desires, presence of comorbidities, and estimated risks and benefits of the procedure (2). Several studies have demonstrated the feasibility of surgically treating lung cancer in elderly patients including octogenarians. Likewise several studies evaluating patients with compromised lung function and other comorbidities have suggested that surgery is feasible in these patients (3,4). What is not clear is what the true limits of age and underlying organ dysfunction is that represent absolute contraindications to surgery. It is likely that improvements in anesthesia and surgical care have allowed older and more high-risk patients to be operated on safely. The use of video assisted thoracoscopy has greatly enhanced our ability to perform surgical resections on these elderly and high-risk patients. The gold standard operation of lobectomy for these patients can potentially be modified in high risk and elderly patients. Several retrospective studies suggest that in the elderly a lesser resection can be equivalent or superior to lobectomy in survival and perioperative morbidity (5). In addition the use of pneumonectomy in these patients should be avoided as the morbidity and mortality is increased significantly (6). It is clear that treatment with stereotactic radiotherapy will play an emerging role in the therapy if these patients. Long-term follow up is needed to truly understand the utility of radiotherapy in high risk and elderly patients. References 1) World Health Organization. Health statistics and health information systems. Available from URL http://www.who.int/healthinfo/survey/ageingdefnolder/en/index.html. 2) Pallis AG, Gridelli C, Wedding U, Faivre-Finn C, Veronesi G, Jaklitsch M, Luciani A, O'Brien M. Management of elderly patients with NSCLC; updated expert's opinion paper: EORTC Elderly Task Force, Lung Cancer Group and International Society for Geriatric Oncology. Ann Oncol. 2014 Jul;25(7):1270-83. 3) Rivera C, Dahan M, Bernard A et al. Surgical treatment of lung cancer in the octogenarians: results of a nationwide audit. Eur J Cardiothorac Surg 2011; 39: 981–986. 4) Zhang R, Ferguson MK. Video-Assisted versus Open Lobectomy in Patients with Compromised Lung Function: A Literature Review and Meta-Analysis. PLoS One. 2015 Jul 6;10(7) 5) Cheng YD, Duan CJ, Dong S et al. Clinical controlled comparison between lobectomy and segmental resection for patients over 70 years of age with clinical stage I non-small cell lung cancer. Eur J Surg Oncol 2012; 38: 1149–1155. 6) Zuin A, Marulli G, Breda C et al. Pneumonectomy for lung cancer over the age of 75 years: is it worthwhile? Interact Cardiovasc Thorac Surg 2010; 10: 931–935.
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ED06.04 - Pulmonary (ID 1797)
15:20 - 15:40 | Author(s): G. Silvestri
- Abstract
- Presentation
Abstract not provided
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Author of
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ORAL 32 - EGFR WT and MT Targeting (ID 144)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K.J. O'Byrne, D.R. Gandara
- Coordinates: 9/09/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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ORAL32.01 - Tumor Genomic Analysis from LUX-Lung 8: A Phase III Trial of Afatinib versus Erlotinib in Squamous Cell Carcinoma of the Lung (ID 1401)
16:45 - 16:56 | Author(s): A. Ardizzoni
- Abstract
- Presentation
Background:
Overexpression of EGFR and other ErbB receptors, and/or dysregulation of their downstream pathways are implicated in the pathogenesis of squamous cell carcinoma (SCC) of the lung, generating interest in exploring EGFR/ErbB-targeted agents in this setting. Recent analyses from the global LUX-Lung 8 trial (n=795) in patients with SCC of the lung demonstrated that second-line afatinib (an irreversible ErbB family blocker) conferred overall survival (OS; median 7.9 vs 6.8 months; HR [95% CI] 0.81 [0.69‒0.95]; p=0.008) and progression-free survival (PFS; median 2.6 vs 1.9 months; HR [95% CI] 0.81 [0.69‒0.96]; p=0.010) benefit over erlotinib (a reversible EGFR inhibitor). To assess biomarkers for efficacy for these agents in SCC we conducted an exploratory analysis using archival tumor tissue collected at time of study entry.
Methods:
Among all randomized patients, samples were retrospectively enriched for those from patients with PFS >2 months and appropriate controls (PFS ≤2 months; Figure 1) and were selected for analysis using the Foundation Medicine (FM) FoundationOne™ next-generation sequencing (NGS) platform (n=433); 300 cancer-related genes were analyzed for copy number alterations (CNAs), rearrangements and single nucleotide variants (SVs). Preliminary results from the 238 samples analyzable so far (~30% of the randomized patients), focusing on genomic alterations of EGFR and their potential association to survival endpoints PFS and OS, are presented.
Results:
Fourteen EGFR SVs (5.8%) were detected of which 10 were novel with unknown clinical significance (Figure 1). Figure 1 Four had been previously reported; 2 (E114K [afatinib arm], Q1021* [erlotinib arm]) occurred in the non-kinase domains and 2 (L861Q [afatinib arm], L858R [erlotinib arm]) in the kinase domain. The frequency of EGFR CNAs (n=15 [6.3%]; afatinib: 9; erlotinib: 6) was also low. At the time of these ongoing analyses, these low frequencies of EGFR mutations/amplifications were deemed not to be associated with the observed improvements in PFS and OS. Genomic alterations aggregated across two key gene groups (ErbB and FGF families) and their association with survival outcomes will be presented.
Conclusion:
The frequency of EGFR genomic aberrations in the samples tested was low. Based on this analysis of a subgroup of patients, PFS and OS improvements conferred by afatinib in LUX-Lung 8 were not driven by the presence of activating EGFR mutations or amplifications and may be related to afatinib’s ability to inactivate multiple aberrant signaling cascades associated with, and downstream of, ErbB receptors.
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