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R. Pirker
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GR 04 - Problems in Advanced Metastatic Disease (ID 18)
- Event: WCLC 2015
- Type: Grand Rounds
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 4
- Moderators:K. Kelly, R. Pirker
- Coordinates: 9/09/2015, 14:15 - 15:45, 702+704+706
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GR04.01 - Case of a Patient with EGFR Mutation Positive Disease and Two Small Brain Metastases (ID 1844)
14:15 - 15:45 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Abstract:
Non-small-cell lung cancer (NSCLC) is the leading cause of brain metastases. The development of brain metastases in this group of patients represents an important public health issue, as 20-40% of NSCLC patients present with or will develop brain metastasis during the course of their treatment. The prognosis of NSCLC patients with brain metastases is generally extremely poor and brain metastases have a major impact on quality of life. The incidence of brain metastases has been increasing over time as a consequence of better neuroimaging modalities and also prolonged survival in the locally advanced and metastatic setting with improved therapies. This is particularly relevant in the group of patients with somatic aberrations within driver oncogenes, such as epidermal growth factor receptor (EGFR) as targeted therapy using tyrosine kinase inhibitors (TKIs) are producing high response rates and progression free survival. Patients with EGFR mutations therefore represent a population at higher risk of brain metastases than the overall NSCLC population, with a risk of developing intra-cranial disease as the first site of progression in approximately 20-30%, and a lifetime risk >50%. Of note, brain metastases in this group of patients present more and more in the context of well controlled systemic disease and are more likely to be treatable than in the historic paradigm where brain metastases developed in concert with progressive multi-organ metastatic disease.Furthermore, there is a suggestion that the prognosis of EGFR mutated patients and brain metastases is better compared to wild type . In the context of stable thoracic and systemic disease treatment options for oligometastatic brain disease include; surgery, stereotactic radiotherapy, whole brain radiotherapy, and systemic treatments. Surgery can play an important role in patients with brain metastases and particularly patients with mass effect from a large symptomatic lesion. Randomised controlled trials with single brain metastases have demonstrated that the addition of surgery to WBRT improves survival. Stereotactic radiosurgery (SRS) is increasingly used as the sole treatment rather than as a ‘booster therapy’ in addition to WBRT to improve local control. Typically, SRS is reserved for patients with controlled extracranial disease and life expectancy >6 months, 1 to 4 brain metastases less than 3cm in maximum diameter. Treatment with EGFR TKIs is generally considered in patients with EGFR mutations but the evidence to support the optimal sequencing with local therapies is limited. In my talk I will discuss the following points: • Risk of developing brain metastases in EGFR mutated NSCLC • Prognostic factors (including EGFR mutation) • The role of local treatment (SRS, WBRT and neurosurgery) • The role of prophylactic cranial irradiation • The role of systemic treatment • Future directions
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GR04.02 - Leptomeningeal Carcinomatosis (ID 1845)
14:15 - 15:45 | Author(s): R. Soo
- Abstract
- Presentation
Abstract:
Leptomeningeal disease is a severe neurologic complication that can be seen in up to 5% of patients with cancer and it is more commonly seen in patients with lymphoma, breast cancer, melanoma and lung cancer. It usually presents in approximately 70% patients with metastatic and progressive disease but may also be the first manifestation of cancer in 10% of cases. With improved diagnostic methods and longer survival of patients with advanced stage non-small cell lung cancer (NSCLC), the incidence of leptomeningeal disease has increased. The diagnosis of leptomeningeal disease is usually established by cytological examination of the cerebrospinal fluid (CSF) or by characteristic changes seen on gadolinium enhanced magnetic resonance imaging (MRI). Furthermore MRI provides anatomic information that may be useful in identifying sites for local radiotherapy treatment. Prognosis is generally poor, especially in patients with poor performance status, multiple, serious or major neurological deficits, bulky CNS disease, and CSF block. Factors associated with a better prognosis include good performance status, absence of major neurological deficits, minimal systemic disease, absence of CSF block and the availability of reasonable systemic therapies. Management principles include early diagnosis and achieving systemic control with the aim of preserving or improving neurological status, improving quality of life and prolonging survival, taking into account the burden of systemic disease, intracranial metastasis and the expected prognosis. Currently there is no standard treatment for leptomeningeal disease in patients with NSCLC and options include intra-thecal chemotherapy, systemic chemotherapy, molecular targeted therapy, and radiotherapy. Although the benefit of intra-thecal chemotherapy has not been proven in randomized controlled studies, it is commonly used as it provides local therapy with minimum systemic toxicity and high drug concentrations can be achieved. It has been noted that intra-thecal chemotherapy is ineffective for bulky meningeal disease as intra-CSF agents can only penetrate 2-3mm into such lesions. Retrospective studies in patients with NSCLC harboring sensitizing mutations in the epidermal growth factor receptor (EGFR) gene or rearrangement in anaplastic lymphoma kinase (ALK) gene suggest EGFR or ALK tyrosine kinase inhibitors is an attractive treatment option. Radiotherapy is used to in the treatment of bulky disease and in patients with CSF flow abnormalities. Radiotherapy is also indicated in symptomatic sites and also in the treatment of cauda equine syndrome and cranial neuropathies. Craniospinal irradiation is rarely administered, as it is associated with significant systemic toxicities and leucoencephalopathy. Several case examples will be presented and the clinical presentation, diagnostic assessment and management will be discussed. The role of molecular targeted agents such as the EGFR and ALK tyrosine kinase inhibitors will also be reviewed. The development of novel systemic agents especially molecular targeted agents with improved CNS penetration and anti-tumor activity is urgently required.
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GR04.03 - Systemic Treatment with Organ Failure (ID 1846)
14:15 - 15:45 | Author(s): P. Wheatley-Price
- Abstract
- Presentation
Abstract:
For patients with lung cancer, choices of systemic therapy are informed by clinical research. These guide the patient and clinician as to the gold standard options when facing their disease. However many patients seen day to day in the clinic are not eligible for clinical trials due to one factor or another, and therefore the applicability of standard of care options has a less solid evidence base. In a recent analysis of 528 newly diagnosed stage 4 NSCLC patients seen in consultation by medical oncologists, only 55% received systemic treatment [1]. Further, when simple and limited generic clinical trial inclusion criteria were applied to these patients, only 27% would have been ‘trial eligible’ [2]. In a review of selected recent practice changing chemotherapy, targeted therapy and immunotherapy trials, patients with significant renal impairment, hepatic impairment or cardiac impairment would have been excluded [3-6]. Therefore how should clinicians and patients approach making decisions about systemic therapy in the presence of organ failure, given the lack of available evidence? This abstract seeks to provide guidance on a reasonable approach to patients with lung cancer and organ failure. These issues should be discussed in a multi-disciplinary format, with specific interaction with specialists related to the particular organ failure (nephrology, hepatology, cardiology etc.), in addition to a specialist oncology pharmacist if the decision is made to proceed with therapy. Patients should be fully informed regarding relative benefits and harms from therapy, the consequences of declining therapy, and that proceeding with treatment will almost certainly not be based on level one evidence. Consideration should be given to early palliative care specialist input, and advance care planning. Understanding the cause and prognosis of the organ failure is self-evidently important. This abstract restricts discussion to patients with pre-existing organ failure, rather than organ failure secondary to the malignancy. In a recent review of clinical indicators of 6-month mortality in advanced non-cancer illnesses, Salpeter and colleagues evaluated heart failure, dementia, geriatric failure-to-thrive syndrome, hepatic cirrhosis, chronic obstructive pulmonary disease and end-stage renal disease. This list represented approximately 70% of the non-cancer diagnoses on admission to hospice [7]. Clearly not all patients with these conditions die within 6 months, and the authors identified common and disease specific prognostic indicators, including poor PS, malnutrition, comorbid illness and organ dysfunction. In the cancer clinic, the clinician must understand the natural course of the organ failure pathology. For patients with liver, kidney or heart failure who may be waiting for organ transplantation, the diagnosis of lung cancer makes them ineligible for the transplant program. Regarding prognosis of advanced organ failure, the United States Renal Data System (USRDS) Annual Report for patients receiving hemodialysis for end-stage renal disease, describes 3-year survival as 52%, and 61% for patients receiving peritoneal dialysis. The risk of death is particularly high in the first year of hemodialysis, with rates reported up to 25%. The Canadian Organ Replacement Register Annual Report describes a 5-year survival for patients on dialysis of approximately 43% (www.cihi.ca/corr ). For patients with end-stage heart failure, the 1-year survival is approximately 50% [8], which is not dramatically different to patients with stage 4 NSCLC receiving 1[st] line chemotherapy. The prognosis of patients with liver cirrhosis is variable, depending on severity, etiology and the presence or absence of complications. The MELD score (Model for End-Stage Liver Disease) is used to assess the severity of chronic liver disease [9], as an alternative to the Child-Pugh scoring system. Salpeter et al reported patients with decompensated liver failure (the presence of complications of cirrhosis) may have a median survival <6 months if associated with high MELD scores. An understanding of competing morbidities therefore clearly plays an important role in understanding the role systemic therapy plays in lung cancer. In assessing the need for adjuvant chemotherapy in patients with early stage disease, for patients with organ failure it is highly likely that any benefit from chemotherapy (approximately 5%) will be outweighed by the competing risks of the comorbid condition. After assessing patients with lung cancer, in the multi-disciplinary context and taking into account the issues discussed, the decision may still be to proceed with therapy. This should be on the understanding of the relative lack of data, and then a choice of regimen based on an understanding of the drug metabolism, with appropriate dose adjustments after dialogue with an oncology pharmacist. Table 1 outlines common lung cancer drugs and their route of elimination, and recommendations on use in renal or hepatic impairment. For patients receiving dialysis, there is variation in advice as to timing of adminstration relative to dialysis. This information and tabular information is taken from product monographs and selected references [10,11]. Data on efficacy for these drugs in these scenarios is largely limited to case reports. In conclusion, lung cancer patients with organ failure represent a population excluded from clinical trials and with a limited evidence base. The competing morbidity and mortality significantly mitigate against potential benefits from anti-cancer systemic therapy. The newer generations of targeted therapies and immunotherapies may be easier to deliver, but again limited data exists. Clinicians should discuss these cases in a multi-disciplinary environment, and early intervention from palliative care specialists may be particularly appropriate.
References : 1. Brule S, Al-Baimani K, Jonker H, et al: Palliative chemotherapy (CT) for advanced non-small cell lung cancer (NSCLC): Investigating disparities between patients who are treated versus those who are not. J Clin Oncol 33, 2015 2. Al-Baimani K, Jonker H, Zhang T, et al: Are clinical trial eligibility criteria an accurate reflection of a real world population of advanced lung cancer patients, World Conference on Lung Cancer. Denver, 2015, pp Abstract 1398 3. Gettinger SN, Horn L, Gandhi L, et al: Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 33:2004-12 4. Mok TS, Wu YL, Thongprasert S, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947-57, 2009 5. Schiller JH, Harrington D, Belani CP, et al: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92-8, 2002 6. Shaw AT, Kim DW, Nakagawa K, et al: Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368:2385-94 7. Salpeter SR, Luo EJ, Malter DS, et al: Systematic review of noncancer presentations with a median survival of 6 months or less. Am J Med 125:512 e1-6 8. Friedrich EB, Bohm M: Management of end stage heart failure. Heart 93:626-31, 2007 9. Kamath PS, Kim WR: The model for end-stage liver disease (MELD). Hepatology 45:797-805, 2007 10. Janus N, Thariat J, Boulanger H, et al: Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients. Ann Oncol 21:1395-403 11. Brandes JC, Grossman SA, Ahmad H: Alteration of pemetrexed excretion in the presence of acute renal failure and effusions: presentation of a case and review of the literature. Cancer Invest 24:283-7, 2006Drug Elimination Liver Renal Cisplatin Renal N/A ↓ depending on CrCl Caboplatin Renal N/A Calvert Formula Docetaxel Liver Adjust N/A Pemetrexed Renal Caution in severe dysfunction avoid if CrCl <45 Paclitaxel Liver Adjust N/A Gemcitabine Urine (inactive) Adjust by Bilirubin Caution Vinorelbine Liver Adjust by Bilirubin N/A Gefitinib Liver Caution Caution if CrCl <20 Erlotinib Liver Caution N/A Afatinib Liver Caution Caution if CrCl <30 Crizotinib Liver Adjust Caution if CrCl <30 Ceritnib Liver Adjust Caution if CrCl <30 Bevacizumab Reticulo-endothelial system Not involved Not involved Nivolumab Biochemical degradation No effect in mild impairment no effect if CrCl>/=15
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GR04.04 - A Case of Recurrent Clotting in Lung Cancer Despite Initial Anticoagulation (ID 1847)
14:15 - 15:45 | Author(s): R. Rosovsky
- Abstract
- Presentation
Abstract not provided
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Author of
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ORAL 16 - Clinical Care of Lung Cancer and Advanced Biopsies (ID 115)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:J.W. Neal, Q. Zhou
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 2a-3b
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ORAL16.04 - Discussant for ORAL16.01, ORAL16.02, ORAL16.03 (ID 3318)
10:45 - 12:15 | Author(s): R. Pirker
- Abstract
- Presentation
Abstract not provided
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-099 - nab-Paclitaxel as Maintenance Therapy in Patients with Squamous Cell NSCLC (ABOUND.sqm) (ID 3122)
09:30 - 17:00 | Author(s): R. Pirker
- Abstract
Background:
Patients with squamous cell (SCC) non-small cell lung cancer (NSCLC) may be at risk of poorer outcomes and have fewer treatment options than those with other histologies. Furthermore, no randomized studies have demonstrated the benefit of maintenance therapy in these patients. In a phase III trial, first-line treatment with nab-paclitaxel plus carboplatin (nab-P/C) demonstrated a 68% improvement in the overall response rate (ORR; 41% vs 24%; P < 0.001) and a trend toward improved overall survival (OS; median, 10.7 vs 9.5 months; HR 0.890; P = 0.310) compared with solvent-based paclitaxel plus C in a subset of patients with advanced SCC NSCLC (Socinski et al. Ann Oncol. 2013;24:2390-2396). An exploratory analysis of the phase III trial demonstrated that therapy with nab-P/C beyond 4 cycles of first-line treatment was effective in the subset of patients with SCC NSCLC who did not progress (from the time of randomization, median progression-free survival [PFS] and OS were 6.8 and 13.8 months, respectively), and no new safety signals were noted (Socinski et al. IASLC 2013 [abstract 3438]). In the open-label, multicenter phase III ABOUND.sqm trial, the efficacy and safety of nab-P maintenance therapy after nab-P/C induction therapy will be evaluated in patients with advanced SCC NSCLC.
Methods:
During the induction part of the study, approximately 540 patients will be treated with 4 cycles of nab-P 100 mg/m[2] intravenously (IV; 30-minute infusion) on days 1, 8, and 15 plus IV C AUC 6 on day 1 every 21 days. Patients with a complete response (CR), a partial response (PR), or stable disease (SD) will be eligible for maintenance. In the maintenance part of the study, approximately 260 patients will be randomized 2:1 to nab-P 100 mg/m[2] on days 1 and 8 every 21 days plus best supportive care (BSC) or BSC alone until disease progression. Patients will be stratified by disease stage (IIIB vs IV), response to induction therapy (CR/PR vs SD), and ECOG performance status at the end of induction (0 vs 1). Key eligibility criteria include histologically or cytologically confirmed stage IIIB/IV SCC NSCLC, no prior chemotherapy for metastatic disease, ECOG performance status ≤ 1, adequate organ function, no active brain metastases, and preexisting peripheral neuropathy grade < 2. ClinicalTrials.gov identifier NCT02027428.Key Endpoints Primary PFS from randomization into the maintenance part of the study Secondary Safety OS from randomization into the maintenance part of the study ORR during the induction and maintenance parts of the study Exploratory Correlation between pretreatment tumor characteristics and response to treatment Association between changes in tumor characteristics and acquisition of resistance to therapy at the time of treatment failure during maintenance Correlation between genetic polymorphisms and treatment efficacy and/or toxicity Healthcare resource utilization during the maintenance part of the study Changes in quality of life
Results:
Not applicable.
Conclusion:
Not applicable.
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PLEN 04 - Presidential Symposium Including Top 4 Abstracts (ID 86)
- Event: WCLC 2015
- Type: Plenary
- Track: Plenary
- Presentations: 1
- Moderators:T. Mok, F.R. Hirsch
- Coordinates: 9/09/2015, 10:45 - 12:15, Plenary Hall (Bellco Theatre)
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PLEN04.02 - Discussant for PLEN04.01 (ID 3613)
10:45 - 12:15 | Author(s): R. Pirker
- Abstract
- Presentation
Abstract not provided
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