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M.M.E. O'Brien
Moderator of
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MS15 - Extending the Limits of Combined Modality Treatment for NSCLC (ID 32)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Combined Modality
- Presentations: 4
- Moderators:M.M.E. O'Brien, I. Tham
- Coordinates: 10/29/2013, 14:00 - 15:30, Bayside 201 - 203, Level 2
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MS15.1 - Targeted Therapy in Combined Modality Therapy for Intrathoracic NSCLC with Activating Mutations (ID 526)
14:04 - 14:27 | Author(s): E. Smit
- Abstract
- Presentation
Abstract not provided
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MS15.2 - Dose Escalation of Radiation in Combined Modality Therapy of NSCLC (ID 527)
14:27 - 14:50 | Author(s): S. Senan
- Abstract
- Presentation
Abstract
Chemo-radiotherapy (CT-RT) is the presently the standard of care in patients presenting with a stage III-N2 NSCLC, with surgery being considered an option in selected patient subgroups [ESMO Guidelines 2013]. Improved local disease control in stage III disease translated into improved overall survival [Auperin A, 2010; Machtay M, 2012]. The best median survival reported to date in a randomized phase III trial of concurrent CT-RT is 28.7 months in RTOG 0617, when concurrent carboplatin-paclitaxel was combined with delivery of 60 Gy in once-daily fractions of 2 Gy [Bradley J, 2013]. At this dose, 25% of patients developed a local failure at 18 months follow-up. Therefore, both the optimization of radiation delivery and dose escalation are areas of active research. Evidence supporting radiation dose escalation comes from retrospective analyses and pooled studies. The randomized RTOG 0617 study compared 60 Gy (in 6 weeks) versus 74 Gy (in 7.5 weeks), in a 2x2 design where patients were also randomized to receive additional cetuximab or none [Bradley J, ASCO 2013]. Analysis of the impact of cetuximab has yet to be reported, but a difference in favor of the 60 Gy arm was seen for progression-free survival (36.6% vs. 26.3% at 18 months), median overall survival (28.7 vs. 19.5 months). A higher incidence of grade 3 esophagitis in the 74 Gy arm (21% vs. 7%, p=0.0003) was not unexpected, but the higher rates of local disease progression (34.3% vs. 25.1%, HR = 1.37, p = 0.0319) was a surprise. The latter raises the possibility of unsafe planning practices being applied when higher (and more toxic) doses have to be delivered. On multivariate analysis, factors predictive of a poorer overall survival were higher radiation doses, higher esophagitis/dysphagia grade, greater gross tumor volume, and heart volumes receiving >5 Gy. While publication of full data from the RTOG 0617 study is awaited, some issues related to toxicity and techniques should considered (below). 1. Improved radiotherapy planning using intensity modulated radiotherapy (IMRT) has permitted some parameters for lung toxicity (V20, mean lung dose) to be improved. However, not all recent or ongoing studies have applied constraints for lung volumes undergoing low-dose irradiation (V5). Furthermore, the choice of chemotherapy may increase lung toxicity, as reported by a recent meta-analysis showing that the risk of radiation pneumonitis is highest after concurrent CT-RT in patients aged >65 years, who also received carboplatin-paclitaxel [Palma D, 2012]. This meta-analysis revealed that predictors of fatal pneumonitis were use of daily dose fractions exceeding 2 Gy, the V~20~ parameter, and lower-lobe tumor locations. 2. Cardiac doses exceeding 5 Gy correlated with poorer survival in RTOG 0617 trial, and future studies must pay more attention to cardiac toxicity. Following concurrent CT-RT, cardiac doses of 45 Gy or higher correlated with myocardial hypoperfusion [Gayed 2006], and a higher risk of ischemic heart disease and cardiac dysfunction was seen patients undergoing CT-RT for left-sided lung cancer [Hardy D, 2010]. 3. After radiation doses of 74 Gy and 86 Gy delivered after chemotherapy, the incidence of bronchial stenosis was 4 and 25%, respectively, (Millar KL, 2005]. This complication may increase in incidence if higher doses of radiation are administered concurrent with chemotherapy. 4. When evaluating the results dose escalation studies, one must also consider the impact of tumor volume on survival in stage III NSCLC. For example, planning target volumes (PTV) correlated significantly with overall survival, with PTV values <350cc, 350-700cc, >700-1050cc and >1050cc having corresponding median overall survivals of 35.6 months (95% CI=0-71.3), 24.2 months (95% CI=18.3-30.2), 15.7 months (95% CI=10.5-20.9) and 10.3 months (95% CI=6.0-14.7), respectively [van Reij E, 2013]. Survival for tumors measuring 350-700cc differed significantly from the groups 700-1050 and >1050 cc (p=0.039 and p=0.002, respectively). In addition, larger tumor volumes are also associated with an increased risk of dying in the first 18 months, independently of T and N stage, but not beyond that time point [Ball D, 2012]. The latter finding suggests that a better characterization of tumor characteristics that correlate with radiocurability should be a research priority. 5. In RTOG 0617, the dose of 74 Gy arm was delivered in 7.5 weeks. A recent meta-analysis suggested that the accelerated delivery of radiation, i.e. delivering a higher higher dose in a shorter overall time, led to superior tumor control [Mauguen 2013]. Such accelerated delivery can be delivered using multiple fractions per day, or larger doses/fraction, both approaches which can increase the toxicity of concurrent CT-RT. For some subgroups of stage III-N2 disease, e.g. large volume tumors, where the benefits of concurrent CT-RT are modest [Wiersma T, 2013], sequential delivery may be a less toxic manner for investigating dose escalation. 6. Tumor volumes not infrequently regress during a course of CT-RT, and may also shift in position during the course of treatment [Lim G, 2011]. Volumetric imaging on modern treatment machines can allow for such changes to be detected, and treatment plans be adapted when required. Many recent clinical studies have not studied this aspect of treatment delivery. With dose escalation in fractions of 2 Gy falling out of favor, some groups are exploring the ‘dose painting’ hypothesis [Bentzen S, 2011]. Briefly, the former assumes that local recurrences arise from relatively radiation-resistant sub-regions; that reliable spatio-temporal mapping of such sub-regions is possible (e.g. using FDG-PET); that boosting radiation delivery to these egions improves local tumor control with acceptable side effects. Others groups are exploring the use of protons to improve local control in stage III NSCLC. A critical evaluation of the results emerging from ongoing trials is required, even if early outcomes from pioneering centers appear promising. Quality assurance data from radiotherapy trials, in which a broad range of institutions participate, reveals that a failure to comply with protocol requirements is associated lead to decreased survival, poorer local control and potentially increased toxicity [Weber DC, 2012].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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MS15.3 - Management of Patients with Oligometastatic/Resectable Stage IV NSCLC (ID 528)
14:50 - 15:10 | Author(s): L. Liu
- Abstract
- Presentation
Abstract
For the past decade, the standard first-line therapy for stage IV non-small-cell lung cancer (NSCLC) patients with adequate ECOG performance status (<2) has been platinum-based doublet chemotherapy with a reported median overall survival (OS) of 8–10 months, which has slightly improved to 12 months with the addition of bevacizumab. More recently, tyrosine kinase inhibitors of epidermal growth factor receptor, gefitinib and erlotinib, and anaplastic lymphoma kinase, crizotinib, have been shown to provide longer progression-free survival (PFS) and fewer side effects as first-line therapy, compared with chemotherapy in patients with certain histological subtypes and activating mutations. However, despite therapeutic developments, palliative treatment is standard for many stage IV NSCLC patients and the prognosis remains poor, with relative 5-year survival rates ≤4%, compared with an average of approximately 17% for all patients with NSCLC. Oligometastatic NSCLC is a subgroup of stage IV NSCLC with a limited number/number of sites of metastatic disease, usually 1–5 metastatic lesions. While only a small subset of patients present with such limited metastases (brain metastasis <50%, adrenal gland metastasis ~7%), they may be suitable for, and achieve long-term survival following, eradication of both the primary and metastatic tumours. For example, reported 5-year survival rates for NSCLC patients with solitary brain or adrenal metastasis who underwent surgical removal of both primary lung and metastatic disease ranged from 7–24% and 25–34%, respectively, which is higher than the average of ≤4% for all stage IV NSCLC patients. In addition to having an adequate performance status, there are additional key prognostic factors for identifying oligometastatic NSCLC patients likely to benefit from aggressive therapy; staging of the metastatic lesions, lymph node involvement and status of the primary lung tumour. A lower number of metastatic sites is predictive of good clinical outcome, with >2 metastatic sites associated with shorter PFS. The organ involved in metastatic spread may also impact clinical outcome as, for instance, patients with brain and adrenal gland metastases are more suitable for surgical intervention compared with bone or liver. Given the importance of number and site of metastatic lesions, positron emission tomography and magnetic resonance imaging are vital for accurate staging of oligometastatic disease. An association between N0 disease and increased long-term survival compared with N1/N2 disease has been observed. For example, following surgical treatment of one cohort of patients with solitary NSCLC adrenal gland metastasis, those with N2 disease had 0% median 5-year survival rate, compared with 52% for N0/N1 patients (P=0.001). Pathologic staging of lymph nodes is therefore critical. The status of the primary lung tumour also impacts clinical outcome, as the primary tumour must itself be resectable. Stage III primary disease is associated with worse survival outcome than stage I or II in patients undergoing surgical excision of brain and adrenal gland metastases, with a reported 5-year survival rate of 0% for stage III, compared with 63% and 77% for stage I and II, respectively. Similarly, patients with oligometastatic disease and a controlled primary site, or ‘oligorecurrance’, have better prognosis than those with an uncontrolled primary tumour. Histological subtype of NSCLC may also impact prognosis in oligometastatic NSCLC, with adenocarcinoma associated with the most favourable outcomes. Although an optimal disease-free interval (DFI) to define synchronous and metachronous disease has not been agreed upon, synchronous oligometastasis is generally associated with poorer survival outcomes. Patients receiving adrenalectomy for oligometastatic NSCLC with DFI ≤6 months had median OS of 12 months versus 31 months for DFI >6 months. Similar results were reported for isolated brain metastasis. Oligometastatic NSCLC is a stage IV cancer and as a guiding principle therapy should be simple and minimally invasive. Furthermore, given the diffuse nature of this disease state, management should ideally involve a multidisciplinary team as the primary and metastatic cancer must be treated, requiring a wide range of expertise. Surgery and radiosurgery (stereotactic radiosurgery [SRS] in the brain and stereotactic body radiotherapy [SBRT] in extracranial sites) are the two most common methods of tumour ablation. In general, radiosurgery is less invasive than surgery and is therefore useful for patients ineligible for surgery. Additionally, evidence suggests SBRT may be more applicable to limited extracranial metastasis to multiple organs compared with surgery. The treatment of limited brain metastases has been evaluated through several randomised clinical trials. Surgical resection plus whole brain radiotherapy (WBRT) of oligometastasis in the brain led to significantly prolonged OS compared with WBRT alone – as high as 40 weeks in one trial, compared with 15 weeks for WBRT (P<0.01). Further, a study of SRS with WBRT in patients with 1–4 brain metastases showed improved survival outcomes for patients with solitary brain metastases and improved clinical outcomes for patients with >1 site of metastatic disease, compared with WBRT alone. Overall, SRS plus WBRT is considered an acceptable choice for those patients with limited brain metastasis who are not suitable for surgery. Adrenalectomy is the standard of care for adrenal gland metastases, with OS ranging from 11–31 months. There have been no randomised trials of the use of SBRT in the adrenal gland setting, although one retrospective study reported OS of 23 months for isolated adrenal metastases treated with SBRT. Further, a recent review article of extracranial oligometastatic disease from various primary cancers suggests that survival following SBRT compares favourably to surgery. One of the key challenges for the management of oligometastatic NSCLC is continuing to improve diagnosis and prognostic factors to more accurately identify those patients with oligometastatic NSCLC who are likely to benefit from ablative treatment, as well as distinguish truly isolated metastatic disease from early-stage metastasis that later develops into widely disseminated disease. Continuing advances in imaging technology will play a role in refining diagnosis and prognosis. From a treatment perspective, challenges include cognitive problems associated with WBRT and the current lack of randomised trial data comparing surgery, radiosurgery and standard of care. To this end, there are several ongoing clinical trials, such as the randomized SABR-COMET study, which compares palliative radiation with stereotactic ablative radiation for ≤3 metastatic tumours to any single organ.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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MS15.4 - Surgery after Induction Chemo/Radiation Therapy (ID 529)
15:10 - 15:30 | Author(s): W. Weder
- Abstract
- Presentation
Abstract not provided
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MS25 - Translating Research into Practice (Applied Statistics) (ID 42)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Statistics
- Presentations: 4
- Moderators:M.M.E. O'Brien, R. Stephens
- Coordinates: 10/30/2013, 14:00 - 15:30, Bayside Gallery B, Level 1
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MS25.1 - Defining the Gold Standard: PFS v OS (ID 579)
14:05 - 14:25 | Author(s): K. Hotta
- Abstract
- Presentation
Abstract
Approval of most new agents for advanced non-small-cell lung cancer (NSCLC) has been based on prolongation of OS, representing a direct measure of clinical benefit, in randomized clinical trials. Recently, however, as we have more opportunity to obtain trial results showing “significant improvement in PFS without any OS benefit”, most investigators feel that the assessment of OS may become of limited use and that PFS must be surrogate endpoint for assessing the efficacy of an experimental agent in NSCLC. Originally, PFS is quite different from OS since it is subjective, but not a direct measure of clinical benefit. Progression is often asymptomatic, and it is not always clinically relevant. To use PFS as surrogate endpoint, its validity should be statistically evaluated. In the pooled analysis using individual patient data of randomized trials comparing first-line docetaxel with vinca-alkaloids, Buyse et al. showed relatively weak PFS-OS correlation [BMJ open 2013;3:e001802]. So far, there seem no other large-scaled validation studies investigating the surrogacy of PFS for OS endpoint with formal statistical approach. Thus, PFS has not yet been a statistically acceptable surrogate endpoint for OS in patients with metastatic NSCLC. Now, what could we interpret “significant improvement in PFS without any OS benefit”? Also, what would be the clinically meaningful endpoint in advanced NSCLC? The literature-based study was conducted to assess the PFS-OS relationship with the data of the phase III trials investigating molecular-targeted agents in advanced NSCLC [Lung Cancer 2013;79:20]. It showed a strong PFS-OS correlation only in trials where subsequent therapy was conducted less frequently, whilst trials with a higher proportion of use of subsequent therapy had weaker association. The study concluded that 1) the relationship between PFS and OS is originally strong enough to support potential surrogacy of PFS, but that 2) given the observation that increasing use of effective salvage therapies could affect the PFS-OS association, improvement in PFS without any OS benefit does not mean the experimental agent fails to have a true clinical benefit. That is, a potentially true OS benefit by an experimental agent would have been seen without any confounding if no subsequent therapy had been given. This theory is called “explanatory approach”, supporting the use of PFS as a clinically meaningful outcome. Rather, there is an opposite opinion, suggesting the observed difference in OS would be considered the measure of clinical benefit, regardless of subsequent therapies, provided that they follow the current standard of care. This is the pragmatic approach [JCO 2011;29:2439]. The observed difference in OS, of course, will be expected smaller by the subsequent therapy than one would see if it was not available, leading to the need of a large sample size to detect such differences. But, according to the pragmatic approach, such potentially attenuated but actually observed OS difference should be used for assessing the true clinical benefit of the experimental agent in the given clinical setting under reflecting the clinical reality of available subsequent treatments. Recently, ASCO discussed what would be clinical meaningful outcome in advanced NSCLC without EGFR or EML4-ALK mutations, and provided draft recommendations as follows: 1) survival after first line therapy is relatively short, and OS is a feasible endpoint although the effects of the experimental agent on OS can be clouded by treatments administered after the period of therapy, and 2) clinical trials should aim to improve OS by a minimum of 25% as compared with standard therapy. ASCO seems to support the importance of measuring OS rather PFS, in favor of the pragmatic approach. Even in the first-line metastatic colorectal cancer, though PFS has already been established as a surrogate for OS in the 90’s, its surrogacy was reappraised using individual patient data between 1997 and 2006 because of the advance in the treatment during the last decade and recent improvement of OS [JCO 2013 (suppl;abstr 3533)]. Surprisingly, the PFS-OS relationship was not as strong as was seen in the 90’s. The study concluded that in modern metastatic colorectal cancer trials where SPP exceeds time to first progression, the treatment effects on PFS do not reliably predict those on OS. It seems that even though PFS was once accepted as a suitable surrogate for OS, its validity should be assessed repeatedly along with the advances especially in the post-progression treatment, which also supports the concept of the pragmatic approach. Regarding the regulatory considerations, the FDA stated OS should be considered the standard clinical benefit endpoint and that it should be used to establish the efficacy of a treatment in metastatic NSCLC, although it can also consider PFS for regulatory decision of drug approval based on the population. Some of the abovementioned findings potentially support the rationale of the pragmatic approach, stressing the importance of a possibly attenuated, but actually observed OS difference. However, this theory is unlikely to be applied in more recent trials investigating specific targeted therapies including EGFR-TKIs or ALK inhibitors, because no OS difference would be arguably obtained due to a quite high level of crossover inevitably for the ethical reason. Thus, under the special situation where i) an experimental agent has theoretically been considered to target specific molecules, and ii) the earlier trials showed dramatic effect, this possibly high proportion of crossover can compromise the ability to assess clinical benefit, and also lead to the unrealistic sample size to detect significant OS difference. Rather, in this condition, whether both large magnitude of PFS advantage and great OS advantage compared with historical control can be obtained would be more important than the conventional assessment of OS difference between the arms. In conclusion, the goals of any new cancer treatment are to offer patients a true clinical benefit. PFS has not yet been formally accepted as a valid surrogate for the OS endpoint in advanced NSCLC, and its surrogacy will be addressed by each drug mechanism of action and patient population. Finally, OS remains the primary endpoint of clinical trials, except in a situation where agents targeting specifically driver oncogenes are being evaluated with anticipation of high level of crossover.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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MS25.2 - Statistical Requirements for Screening Trials (ID 580)
14:25 - 14:45 | Author(s): L. Billingham
- Abstract
- Presentation
Abstract
A screening programme is a set of procedures that can be applied to an asymptomatic population to enable early detection and treatment of disease. The success of the programme is dependent on this early intervention reducing morbidity and mortality associated with the disease. There has been much research to develop and assess potential screening programmes for lung cancer. In particular, there are a number of major clinical trials such as the National Lung Screening Trial in the United States, the United Kingdom Lung Cancer Screening Trial and the Dutch-Belgian NELSON trial, that assess the effectiveness of screening a high risk population with low dose computed tomography scans to reduce mortality from lung cancer. The key elements of any screening programme are: (i) identification of the target population for screening, (ii) the screening test that will be used to classify patients as likely or unlikely to have the disease, (iii) the frequency of applying the screening test, (iv) the diagnostic test that will be used to determine whether people are truly diseased or not, (v) the treatment that will be available for those diagnosed early. These choices will impact on the statistical design. The research question may be whether to introduce screening, to determine the frequency of screening, to identify the appropriate target population for screening or whether to add an additional screening tool to an existing screening modality. Randomised controlled trials are the gold standard for assessing a screening programme as they overcome major biases specific to screening namely lead-time bias, length bias, over-diagnosis bias and selection bias. The usual trial design parameters are important but special statistical issues arise in relation to screening trials. Statistical inferences should only be made back to the eligible population defined for the trial so the choice of eligibility criteria is important. Screening interventions can cause harm to individuals that are potentially disease-free so the target population is usually those who are at high risk of disease. Interventions such as CT scans which have both a relatively high risk and high level of harm should be targeted at a high risk population whilst those that are low risk to the individual such as sputum cytology could be targeted at a wider population. Harms also include the inconvenience and psychological effects of a false positive result. A high risk population is usually defined in terms of pack-years of smoking and time since quitting and simple patient characteristics such as age. Statistical models that predict risk of disease could enhance the identification of a high risk population but the accuracy of prediction should be considered in relation to its impact on the trial. The primary outcome measure to assess benefit of a lung cancer screening programme should be lung cancer specific mortality. Duration of follow-up is an important design parameter. It needs to be long enough to allow for the time lag before the impact of screening becomes apparent and not so long after the cessation of screening as to include a period of time when screening would have lost its impact. Appropriate statistical analysis of the primary outcome measure is essential to properly evaluate the benefits of screening. Typically the screening intervention will be compared to the control arm in terms of its ability to reduce cumulative mortality. If this is calculated over the entire period of screening and follow-up then the benefit may be underestimated. Comparing time-specific mortality rates is the recommended approach [1]. The analysis is also complicated by the problems of non-attendance and contamination but methods have been proposed to adjust for these [2]. Sample size calculations involve key design parameters including hypothesised mortality reductions, expected compliance and contamination, number of screening rounds and length of follow-up [3]. The accuracy of the screening test to predict disease in asymptomatic people is not only important for the feasibility and ethics but will also impact on sample size as inaccurate predictions will dilute the potential benefit of screening. Screening tests, such as those that involve biomarkers measured on a continuous measurement scale, should be rigorously developed and validated before assessing their clinical utility within a randomised controlled trial environment. References [1] Hanley JA; Measuring mortality reductions in cancer screening trials; Epidemiologic Reviews 2011; 33: 36-45. [2] Baker SG, Kramer BS, Prorok PC; Statistical issues in randomised trials of cancer screening; BMC Medical Research Methodology 2002; 2: 11. [3] Prorok PC, Marcus PM; Cancer screening trials: nuts and bolts; Seminars in Oncology 2010; 37(3): 216-223.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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MS25.3 - Cost-Effectiveness of Modern Therapies (ID 581)
14:45 - 15:05 | Author(s): N. Leighl
- Abstract
- Presentation
Abstract
The growing number and rising costs of modern lung cancer therapies have brought the issue of cost and cost effectiveness to the forefront of clinical practice. While personalized medicine improves outcomes in specific subgroups, sparing others from ineffective costly treatment and toxicity, it can be challenging to incorporate into economic analyses. Defining the target population for the new treatment is key, and then evaluating the costs and benefits of the new intervention compared to the previous standard. However, the definition of molecular populations for targeted therapies has emerged as an important consideration when considering whether or not to adopt a new targeted therapy. The cost of biomarker testing can have a major impact on healthcare costs, and many countries are struggling with how to best incorporate the "hidden" costs of personalized medicine into adopting new targeted therapies. Focusing only on the target population, comparing the new treatment with standard comparators does not incorporate the costs of biomarker testing, or need for repeat biopsies for successful testing, but will be a better reflection of the benefit of the new treatment in that population. Comparing a test-and-treat strategy to a strategy without testing or the new therapy allows incorporation of the costs of testing, but has some important challenges. Biomarker frequency is a key driver in these analyses, with smaller populations as a particular challenge, such as ALK positive nonsmall cell lung cancer. Presenting the cost of both a test-and-treat strategy alongside an evaluation of the cost effectiveness of therapy in the target population may be a better way to illustrate the impact of a novel treatment, especially when the target population is small, while acknowledging the incremental financial burden of biomarker testing in cancer. This may allow new therapies to compete with current alternatives on a comparable footing, and not underestimate the impact of a new treatment in a small subgroup. It would also permit the development of more effective and cost-efficient screening methods for the desired target population. It is important to recall that technological methods and costs involved in biomarker testing and molecular analysis are rapidly changing, and should be revisited over time. The technological methods used to identify molecular abnormalities in cancer, such as sequencing and antibody development, are changing rapidly along with associated costs. Thus less expensive or more efficient methods (e.g. multiplex testing) may be more affordable compared to more labor-intensive methods used in initial clinical trials. For example, immunohistochemical techniques may replace more expensive methods, allowing more jurisdictions to take up testing and treatment of new therapies.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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MS25.4 - Assessing New Treatments for Lung Cancer - Regulatory and Cost-Effectiveness Implications (ID 582)
15:05 - 15:25 | Author(s): S.R. Hill
- Abstract
- Presentation
Abstract
Over the last several years, there have been a number of new classes of drugs approved for the management of lung cancer. Regulatory pathways are evolving in many ways – for example, to recognize that targeted therapies, such as the EGFR inhibitors, will require evaluation of the drug alongside a diagnostic test; or that the increasing specificity of targets may result in smaller and shorter trials with different endpoints; or that regulatory authorities might identify potential significant advances in therapy by the use of special evaluation pathways, such as the ‘breakthrough’ therapy designation from the US FDA. Sometimes the trials now also measure quality of life outcomes or patient preferences. But these trials are still fundamentally designed to ask the ‘regulatory’ question – can the new product work – as well as assessing the risk-benefit ratio. But where does this changing regulatory environment leave payers? The information set that is available to guide assessments of value of money generally seems to becomes more limited as the regulators increase the pace of their decision-making. Trials are truncated or treatment groups are crossed over to the new treatment at the earliest possible opportunity, often before there is a confident estimate of the effect size in terms of final clinical outcomes. The ethical imperative to offer access to possibly effective treatments outweighs ensuring adequate trial design to be confident in the estimate of effect. Statistical techniques to ‘adjust’ for limitations in design become more and more complex, and more prone to uncertainty. And at the same time, most countries are still struggling with faltering economies and diminishing health budgets. Patients still want access to the latest treatments, but are less and less willing to pay increasing prices. Payers then have to compare the limited information set available for new drugs with what is known about current treatments. Arguments over the value of differences such as a 1.4 months gain in overall survival compared to existing treatment become conflated with the cost of this gain. That is assuming, of course, that there is a gain in overall survival, which has not been often shown to date in the trials of the new drugs for lung cancer. When high prices and high prevalence are combined, the value-for-money question is rightly raised – why pay so much more for so much uncertainty? Arguments about incremental advances in therapy, innovation and technological developments then dominate the discussion, rather than the appropriate focus on health gain for communities and individuals. So what is the solution? Options suggested include ‘managed entry’ of new products with additional data collection as a condition of price negotiation, ‘paying for performance’ with outcome data collection, or ‘value-based pricing’ that allows a premium for ‘innovation’. However, given the high clinical need for effective treatments, the emphasis should be on getting the best health outcomes for an affordable price, to the community and for individuals.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.
Author of
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MO13 - SCLC I (ID 118)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:C.K. Liam, E.S. Santos
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 201 - 203, Level 2
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MO13.11 - DISCUSSANT (ID 3963)
11:30 - 11:45 | Author(s): M.M.E. O'Brien
- Abstract
- Presentation
Abstract not provided
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P3.10 - Poster Session 3 - Chemotherapy (ID 210)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.10-026 - Outcomes of patients undergoing adjuvant platinum-vinorelbine chemotherapy for resected non-small cell lung cancer (NSCLC) (ID 1566)
09:30 - 09:30 | Author(s): M.M.E. O'Brien
- Abstract
Background
Cisplatin-vinorelbine adjuvant chemotherapy significantly improves survival in resected NSCLC. We evaluated outcomes of patients receiving adjuvant chemotherapy in our institution between 2006-2011.Methods
Outcomes of stage IB -IIIA NSCLC patients who received platinum-vinorelbine following radical lung surgery were collected and analysed to assess overall survival (OS), progression-free survival (PFS), and treatment intensity.Results
53 patients were identified (23:30, M:F), mean age 62, and 35% were adenocarcinoma. Resected stage was 1B-3A, with one-third stage 3A. When tested, EGFR mutation prevalence was 33% (39% never smokers; 61% ever smokers). There was one death from chemotherapy toxicity. Median chemotherapy cycles given was 4. There was no difference in PFS or OS in patients having carboplatin compared with cisplatin. A significantly improved OS in patients that received ≥3 cycles of chemotherapy was observed (HR=0.25, 0.07-0.97, p=0.04). 60.4% patients had relapsed at last follow-up. Radically treatable disease on relapse was detected by surveillance imaging.Conclusion
Our small dataset indicates that four cycles of adjuvant platinum-vinorelbine chemotherapy is deliverable in the real world setting, and that less than 3 chemotherapy cycles is associated with poorer outcomes.
