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M.A. Gubens
Moderator of
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ED 13 - The EGF Receptor and Targeting T790M (ID 13)
- Event: WCLC 2015
- Type: Education Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 4
- Moderators:M. Boyer, M.A. Gubens
- Coordinates: 9/09/2015, 14:15 - 15:45, Mile High Ballroom 1a-1f
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ED13.01 - Biological Background and Controversies (ID 1824)
14:15 - 15:45 | Author(s): B.J. Solomon
- Abstract
- Presentation
Abstract:
The ability to identify and therapeutically target specific mutations (typically exon 19 deletions and L858R) in the Epidermal Growth Factor Receptor (EGFR) gene marked the beginning of personalized medicine for NSCLC. Phase III clinical trials with the EGFR tyrosine kinase inhibitors gefitinib, erlotinib and afatinib demonstrated superiority of these agents over chemotherapy establishing these agents as standard therapy for EGFR mutation positive NSCLC. However, resistance to therapy invariably occurs through multiple, heterogeneous mechanisms of which a secondary gatekeeper mutation in EGFR, T790M, is the most frequent, being identified in 50-60% of patients at the time ofprogression after initial EGFR TKI. EGFR T790M is thought to result in resistance by increasing the affinity for ATP rather than simple stearic hinderance. Recently novel irreversible inhibitors, structurally distinct to earlier generation compounds, have been developed that inhibit T790M while having relatively less potency against wildtype EGFR including rocelitnib (C01686) and AZD9291. Phase I/II studies have demonstrated responses to rocilitinib (CO1686) and AZD9291 in about 60% of patients with T790M positive disease. Preliminary data indicates the degree of response may correlate with the allelic frequency of T790, with greater degrees of responses in patients with higher proportions of T790M. Resistance to these compounds has been described clinically and includes loss of T790M, small cell transformation as well asdevelopment of tertiary mutations C7957 (resistance to AZD9291).
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ED13.02 - Detecting T790M in Blood and Tumor (ID 1825)
14:15 - 15:45 | Author(s): D.L. Aisner
- Abstract
- Presentation
Abstract:
Recent advances in targeted therapies and the molecular analysis of tumor samples have led to recommendations that EGFR mutation testing be implemented as standard of care in non-small cell lung cancer (NSCLC) of non-squamous type. This is in large part because of substantial benefits provided to patients treated with EGFR tyrosine kinase inhibitor (TKI) therapy, particularly those patients whose tumors are positive for activating, sensitizing mutations in EGFR. Despite these benefits, resistance to EGFR TKIs inevitably develops in all cases. The most common molecular mechanism of acquired resistance in this setting, occurring in approximately 50% of cases, is the evolution of a secondary ‘gatekeeper’ mutation which results in p.T790M (T790M). This acquired mutation results in a reduction in affinity of EGFR for the TKIs, while preserving catalytic function of the tyrosine kinase domain, The testing for T790M at the time of progression on TKI has emerged as an important clinical practice, as new-in-class EGFR TKIs demonstrate activity against this subset of resistant tumors. Because T790M initially emerges as a sub-clonal event, technical elements involved in its detection become paramount. Most importantly, achieving a high technical sensitivity to allow for detection of a sub-clonal (low alleleic frequency) phenomenon is critical for assays designed to detect this mutation. Sanger sequencing, for example, lacks the technical sensitivity to adequately identify low variant frequency events, and therefore alternate mechanisms of testing are required. Additional factors requiring major consideration in detection of T790M include potential sampling bias (particularly for the small biopsies or fine needle aspirates that are typically acquired), heterogeneity between multiple progressing lesions, cellular components of post-treatment biopsies, and technical ability to perform tumor enrichment to enhance detection. Genomic alterations resulting in T790M are uncommonly detected prior to TKI therapy, likely owing to the technical sensitivity of assays used to query for the presence of this alteration. Studies employing extraordinarily sensitive assays have demonstrated the presence of T790M as a subclonal event prior to TKI therapy in many tumors. Thus clonal selection under the pressure of TKI is a major mechanism allowing this alteration to be identified in the setting of progression on targeted therapy using less analytically sensitive assays. The secondary implication of this finding is that assays employed for detection of T790M must be adequately sensitive, but not over-sensitive to allow for the appropriate identification of what can best be considered the dominant mechanism of resistance. Others have postulated that highly sensitive detection of T790M prior to therapy could be used to determine a combination therapy approach which effectively prevents the evolutionary advantages of this sub-clone. In the uncommon instance that this alteration is identified at a high level pre-TKI therapy using standard assay approaches (<5% of cases), it can be associated with a germline alteration leading to a genetic predisposition for lung cancer. Recently, there has been great interest in the potential to monitor for the emergence of T790M alterations in the periphery, either via circulating tumor cells or circulating cell-free DNA. This approach is particularly attractive as it reduces requirements for invasive tissue sampling and can allow for a continuous monitoring approach. While the technical elements of liquid biopsy testing have been diversely applied, with very little in the way of consensus on methodology, numerous studies have demonstrated the promise of liquid biopsy approaches for both primary mutation detection as well as evaluation for T790M. In some cases, peripheral detection of T790M was demonstrated substantially before radiographic evidence of progression, a key proof-of-principle that such monitoring could be utilized as an effective approach for disease monitoring. Similar approaches for chimerism analysis or BCR-ABL1 transcript monitoring in the setting of bone marrow transplant or TKI therapy for chronic myelogenous leukemia, respectively, have been very successful. Major challenges still exist for both tissue-based and peripheral blood-based detection of T790M. Determination of the ideal level of assay technical sensitivity required for prediction of response to T790M-directed therapies will be a critical component to the implementation of these drugs in the clinic. In addition, for tissue biopsies, techniques to enhance the tumor cellularity of tested material and to avoid sample bias will need to be further refined. Liquid biopsy techniques, though demonstrating extraordinary promise, are widely divergent in terms of methodologies employed, and further study in this technological space is needed. 1. Arcila ME, Oxnard GR, Nafa K, et al. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clinical cancer research : an official journal of the American Association for Cancer Research 2011;17:1169-1180. 2. Inukai M, Toyooka S, Ito S, et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 2006;66:7854-7858. 3. Kim Y, Ko J, Cui Z, et al. The EGFR T790M mutation in acquired resistance to an irreversible second-generation EGFR inhibitor. Mol Cancer Ther 2012;11:784-791. 4. Majem M, Remon J. Tumor heterogeneity: evolution through space and time in EGFR mutant non small cell lung cancer patients. Transl Lung Cancer Res 2013;2:226-237. 5. Newman AM, Bratman SV, To J, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nature medicine 2014;20:548-554. 6. Oxnard GR, Paweletz CP, Kuang Y, et al. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clinical cancer research : an official journal of the American Association for Cancer Research 2014;20:1698-1705. 7. Paweletz CP, Janne PA. Monitoring cancer through the blood. Cancer 2014;120:3859-3861. 8. Sorensen BS, Wu L, Wei W, et al. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib. Cancer 2014;120:3896-3901. 9. Tartarone A, Lerose R. Clinical approaches to treat patients with non-small cell lung cancer and epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance. Ther Adv Respir Dis 2015. 10. Watanabe M, Kawaguchi T, Isa SI, et al. Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non-Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR. Clinical cancer research : an official journal of the American Association for Cancer Research 2015.
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ED13.03 - How to Make the Best Use of 'Old' Drugs (ID 1826)
14:15 - 15:45 | Author(s): G.R. Oxnard
- Abstract
- Presentation
Abstract:
Acquired resistance to initial EGFR TKI invariably develops in patients with EGFR-mutant lung cancer after a median of 9-14 months. Though acquired EGFR resistance in NSCLC is a clinical condition that is treated and studied worldwide, there has until recently been a paucity of prospective data describing the best practices for managing these patients. In 2014, the first phase III trial studying EGFR-mutant lung cancer with acquired resistance was reported. Presented at ESMO 2014, the IMPRESS trial established platinum doublet chemotherapy as the standard second-line therapy for these patients, with no benefit to additionally continuing EGFR TKI at progression. And yet, even with standard second-line therapy established, there remain questions regarding how to manage patients with progressive disease (PD) on EGFR TKI, questions that will likely grow even more complex should newer agents reach the market. One way of framing this question is to consider the tools we have for managing acquired EGFR resistance, and then to consider how to best utilize them. The following outline provides a brief summary of therapeutic strategies that will be discussed further at WCLC 2015. · Continued TKI after PD - Feasible for a median of 3 months, especially in those with slow or asymptomatic PD (Lo et al, Cancer, 2015; Park et al, ESMO, 2014) · Retreatment with TKI after PD on chemo - 25% RR on a prospective phase II study of 20 patients, but responses were brief with a 3.4 month median PFS (Oh et al, Lung Cancer, 2012) · Afatinib – Limited activity in LUX-Lung 1 trial with 7% RR and 3 month median PFS (Miller et al, Lancet Oncol, 2010) · Afatinib / cetuximab – 29% RR and 4.7 month median PFS, with responses seen regardless of T790M status (Janjigian et al, Cancer Disc, 2014) · Cytotoxic chemotherapy – Cisplatin /pemetrexed has a 34% RR and 5.4 month median PFS after PD on gefitinib (Mok et al, ESMO, 2014) · Erlotinib & bevacizumab – May delay development of PD, but no prospective data for treatment of resistance (Seto et al, Lancet Oncol, 2014) · Erlotinib & crizotinib – Hypothetical option for MET-mediated resistance but requires dose reduction of both (Ou et al, ASCO, 2012) · Nivolumab – 82 patients with prior TKI and chemo treated on CheckMate 057, and there was no OS benefit seen compared to docetaxel (HR 1.18) (Paz-Arez, ASCO, 2015) · Erlotinib & nivolumab – 3 of 20 patients responded (15%) in the phase I study (Rizvi et al, ASCO, 2014) · Brain radiation – For CNS-only progression, radiation followed by restarting TKI can gain additional months of PFS (Weickhardt et al, JTO, 2012) · SBRT or surgical resection – An approach that is hypothesized to debulk a single resistant clone, thus delaying clinical resistance and prolonging the progression-free period (Weickhardt et al, JTO, 2012; Yu et al, JTO, 2013)
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ED13.04 - 3rd Generation EGFR TKI (ID 1827)
14:15 - 15:45 | Author(s): K. Park
- Abstract
- Presentation
Abstract:
The introduction of EGFR TKIs has dramatically changed the natural history of advanced and/or metastatic NSCLC. The objective response rates of 50 to 70% are achieved and overall survival has improved from 4-5 months to over 30 months in EGFRm(+) NSCLC patients. However, unfortunately the patients are not cured of the disease and after a median PFS of 9 to 13 months, the disease comes back eventually with the emergence of acquired resistance(AR) to EGFR TKIs. Mechanisms of AR include target gene modification, activation of bypass tracks or histologic transformation, etc. In approximately 60% of patients, the mechanism of resistance is due to the acquisition of a gatekeeper T790M EGFR mutation. This T790M mutation leads to an enhanced affinity for ATP, thus reducing the ability of ATP-competitive reversible EGFR tyrosine kinase inhibitors, including gefitinib and erlotinib, to bind to the tyrosine kinase domain of EGFR. One strategy to overcome this mechanism of resistance mediated by target gene modification is through the use of more potent, novel, next-generation inhibitors. The ‘2[nd]-generation’ irreversible EGFR inhibitors such as afatinib and dacomitinib, covalent inhibitors of HER family kinases, showed preclinical activity against T790M in vitro. Both agents demonstrated excellent clinical activities in EGFR TKI-naïve patients with EGFR-mutant NSCLC in terms of response rate and progression-free survival as compared to cytotoxic chemotherapy. However, the results of treatment in patients with EGFR-mutant lung cancer who progress on an EGFR TKI are quite disappointing. Studies of afatinib monotherapy among patients with acquired resistance to erlotinib or gefitinib showed a response rate of only 7-8% and a progression-free survival of 3 to 4 months. This result may be due to the fact that physiologic doses of current generation irreversible EGFR TKIs do not fully inhibit EGFR T790M and dose escalation of 2[nd]-generation EGFR inhibitors is limited by on-target inhibition of wild-type EGFR, which leads to EGFR-mediated toxicity (skin rash and diarrhea). The so-called ‘3[rd]-generation’ EGFR TKIs are pyrimidine-based irreversible inhibitors and has mutant-specific activity including T790M mutation while sparing wild-type EGFR. There are several 3[rd]-generation EGFR TKIs under development, e.g., AZD 9291, CO-1686(Rociletinib), HM61713, ASP8273, EGF816, to name a few. The early clinical trials of the 3[rd]-generation EGFR TKIs have demonstrated a promising efficacy in patients with advanced EGFR-mutated NSCLC who have progressed on prior EGFR TKI therapy, including cohorts of patients with EGFR T790M-mutated NSCLC. For CO-1686, the reported overall response rate in the phase 1 study was 59%(27/46) in patients with centrally confirmed EGFR T790M-containing tumors. Median progression-free survival was 13.1 months. Likewise, initial results from the phase I trial of AZD9291 demonstrated a response rate of 61%(78/127) in patients with EGFR T790M positive tumors with median PFS of 9.6 months. Both AZD9291 and CO-1686 have recently been granted Breakthrough Therapy designation by the US FDA based upon results from early clinical studies. Early phase I/II results of HM61713 also showed encouraging anti-tumor activity with objective response rate of 55%(34/62) in T790M positive Korean NSCLC patients and global phase II trial is planned to launch. The early results of EGF816 and ASP8273, another irreversible 3[rd]-generation EGFR TKIs under clinical development, were recently reported and both agents demonstrated encouraging response rates of 50-60% in T790M(+) NSCLC patients after progression on a 1[st] or 2[nd] generation EGFR TKIs. Further studies are ongoing and mature results are awaited. In brief, many of the 3[rd] generation EGFR TKIs currently at various stages of development look so promising with encouraging clinical activities for T790M(+) NSCLC patients esp. in terms of response rate. In general these newer generation EGFR TKIs also have much better toxicity profiles as they spare the wild-type EGFR, e.g., less skin rash, diarrhea or paronychia compared with the 1[st]- or 2[nd]-generation EGFR TKIs though the toxicity profiles are slightly differerent one from another at some aspects. Since the follow-up is rather short we need longer follow up to confirm survival benefits. We certainly have made a significant progress in the management of advanced NSCLC with AR to EGFR TKIs, however, there are still several issues to be investigated to further improve the treatment outcomes, e.g., optimal timing and/or sequence of the 3[rd] generation EGFR TKIs, how to delay or prevent the emergence of resistance to 3[rd] generation agents, CNS progression, management of non-T790M-dependent AR to EGFR TKIs, etc. References Cong CR and Jänne PA. The quest to overcome esistance to EGFR-targeted therapies in cancer. Nat Med. 2013;19(11):1389-1400 Lovly CM and Shaw AT. Molecular Pathways: Resistance to Kinase Inhibitors and Implications for Therapeutic Strategies. Clin Cancer Res. 2014;20(9):2249–56. Jänne PA et al. AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer, N Engl J Med. 2015 Apr 30;372(18):1689-99. Sequist LV et al. Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer, N Engl J Med. 2015 Apr 30;372(18):1700-9. Park K et al. Updated safety and efficacy results from phase I/II study of HM61713 in patients (pts) with EGFR mutation positive non-small cell lung cancer (NSCLC) who failed previous EGFR-tyrosine kinase inhibitor (TKI). PASCO 2015 #8084 Tan D S-W et al. First-in-human phase I study of EGF816, a third generation, mutant-selective EGFR tyrosine kinase inhibitor, in advanced non-small cell lung cancer (NSCLC) harboring T790M. PASCO 2015 #8013 Goto Y et al. ASP8273, a mutant-selective irreversible EGFR inhibitor in patients (pts) with NSCLC harboring EGFR activating mutations: Preliminary results of first-in-human phase I study in Japan. PASCO 2015 #8014T
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Author of
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ORAL 11 - Clinical Trials 1 (ID 100)
- Event: WCLC 2015
- Type: Oral Session
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:A.K. Nowak, F. Detterbeck
- Coordinates: 9/07/2015, 10:45 - 12:15, 702+704+706
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ORAL11.05 - Phase II Trial of Single Agent Amrubicin in Patients with Previously Treated Advanced Thymic Malignancies (ID 1288)
10:45 - 12:15 | Author(s): M.A. Gubens
- Abstract
- Presentation
Background:
Limited treatment options exist for patients with thymic malignancies (TM), and chemotherapy efficacy is often restricted by cumulative toxicity such as neuropathy (taxanes) and cardiomyopathy (anthracyclines). Single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor with minimal cardiac toxicity, was investigated in TM pts in this trial.
Methods:
This was an open-label single drug trial at 2 institutions. Eligible pts had TM (thymoma (T) or thymic carcinoma (TC)) with progression or relapse after at least 1 prior chemotherapy regimen, and adequate organ function including left ventricular ejection fraction (LVEF) of >50%. The initial treatment plan consisted of amrubicin at 40 mg/m[2] IV days 1-3 repeated in 3-week cycles.
Results:
From 7/11 to 4/14, a total of 33 patients (14T/19TC) were enrolled. There were 14 women and 19 men; age range of 30-81 years; 9 Asian, 1 African-American, 1 Hispanic and 22 non-Hispanic White pts. A high rate of febrile neutropenia (FN) led to an amended starting dose of 35 mg/m[2] days 1-3 repeated in 3-week cycles. In total, 7 pts experienced FN with 1 related death. Other grade 3/4 related events included: thrombocytopenia (n=2), neutropenia without fever (n=3), hyponatremia (n=2), hypokalemia (n=2), anemia (n=7), lethargy/fatigue (n=7), perirectal abscess (n=2), palmar-plantar erythrodysesthesia (n=3), syncope (n=2), venous embolism (n=2), and 1 pt each with sepsis, oral abscess, mucositis, chest pain, and epigastric pain. Other toxicities were generally mild and well tolerated. No significant changes in LVEF were noted on serial echocardiograms. There were 6 partial responses (4T/2TC), 21 with stable disease, and 4 with progressive disease (PD) or death at or before first assessment for a response rate (RR) of 18% and a disease control rate (DCR) of 88% (29%/11% RR in T vs TC and 100%/78% DCR in T vs TC). All but 5 patients received at least 4 cycles, and 15 tolerated >10 cycles, with 36 cycles as the highest number to date. Five patients remain on therapy.
Conclusion:
Amrubicin, at 35 mg/m[2 ]IV days 1-3 on a 3-week cycle, shows promise as a single agent in pre-treated patients with thymoma and thymic carcinoma with an 18% RR and no unexpected toxicity. Response rate and disease control rate was higher in the thymoma patients compared to the thymic carcinoma patients. Further exploration of amrubicin as a single drug or in combination is warranted in thymic malignancies.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-079 - Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone as First-Line Therapy for NSCLC (ID 2993)
09:30 - 17:00 | Author(s): M.A. Gubens
- Abstract
Background:
Platinum doublet chemotherapy with or without bevacizumab is the standard first-line therapy for patients with advanced NSCLC without EGFR sensitizing mutations or ALK rearrangement. Pembrolizumab (MK-3475), a humanized monoclonal antibody against PD-1 designed to block the interaction of PD-1 with its ligands PD-L1 and PD-L2, has shown efficacy and a manageable toxicity profile in patients with NSCLC treated at doses ranging from 2 mg/kg every 3 weeks to 10 mg/kg every 2 weeks. In 45 patients with treatment-naive advanced NSCLC treated in KEYNOTE-001, single-agent pembrolizumab has demonstrated a response rate of 26%.
Methods:
KEYNOTE-021 (ClinicalTrials.gov, NCT02039674) is an international, open-label, multi-arm, phase 1/2 trial of pembrolizumab for advanced NSCLC. After establishing the safety and tolerability of pembrolizumab plus carboplatin and pemetrexed in phase 1, a randomized phase 2 cohort comparing the efficacy of pembrolizumab plus carboplatin and pemetrexed with that of carboplatin and pemetrexed has been initiated. Key eligibility criteria for this cohort are previously untreated stage IIIB/IV nonsquamous NSCLC, no sensitizing EGFR mutation or ALK rearrangement, and ECOG PS 0-1. Patients will be randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg Q3W plus carboplatin and pemetrexed at standard doses or carboplatin and pemetrexed alone. Randomization will be stratified by PD-L1 expression determined by immunohistochemistry at a central laboratory (positive [membranous expression in ≥1% of tumor cells] vs negative). Pembrolizumab will be given for 24 months or until progression, intolerable toxicity, or investigator decision. Pembrolizumab may be continued beyond radiographic progression in eligible patients. Carboplatin and pemetrexed will be given for 4 cycles followed by maintenance pemetrexed, alone or with pembrolizumab. Patients allocated to the chemotherapy-alone arm who experience progression may cross over to the pembrolizumab arm of the study. AEs will be monitored throughout treatment and for 30 days thereafter. Response will be assessed every 6 weeks for the first 18 weeks, then every 9 weeks in year 1 and every 12 weeks in year 2. Survival follow-up will occur every 3 months after discontinuation of study treatment. Primary end point is progression-free survival (RECIST v1.1, central review); secondary end points include overall survival, objective response rate, and correlation of PD-L1 expression with antitumor activity. This cohort is currently enrolling patients.
Results:
Not applicable.
Conclusion:
Not applicable.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-089 - Prospective Use of Prognostic Molecular Assay Identifies Patients at Risk for Recurrence and Changes Clinical Management in Early-Stage NSCLC (ID 1497)
09:30 - 17:00 | Author(s): M.A. Gubens
- Abstract
Background:
Adjuvant chemotherapy recommendations depend on identification of early-stage non-small-cell lung cancer (NSCLC) patients at high-risk of recurrence. Current National Comprehensive Cancer Network (NCCN) guidelines use certain clinicopathologic features to make this recommendation for stage Ib-IIa patients. An internationally validated, 14-gene expression assay has been shown retrospectively to better stratify mortality risk in non-squamous NSCLC than conventional staging.
Methods:
Following up on a previously reported cohort of 52 patients, prospective molecular risk-stratification by the 14-gene test was performed in 66 patients with a mean follow up of 20.7 ±14.1 months. Disease-free survival and lung cancer mortality rates were compared between high- and low-risk patients by both molecular risk-stratification and NCCN “high-risk” characteristics.
Results:
Patients with low-, intermediate-, and high-risk based on molecular testing had recurrence rates of 4%, 8%, and 28% (p=.031, Fisher’s exact test) and lung cancer mortalities of 0%, 0%, and 16% (p=.039), respectively. Molecular high-risk was associated with shorter disease-free survival (p=.043, Kaplan-Meier log-rank). Molecular risk assessment was discordant from NCCN “high-risk” features in 15 of 25 stage Ib-IIa patients (60%). NCCN criteria failed to significantly predict either recurrence or mortality with recurrence rates of 8% and 23% (p=.077, Fisher’s exact test) and lung cancer related mortality of 3% and 12% (p=.165) among patients with NCCN low- and high-risk features respectively. Molecular high-risk scores changed adjuvant chemotherapy recommendations in 3 of 10 (30%) patients who otherwise did not meet NCCN criteria for adjuvant chemotherapy.
Conclusion:
This study demonstrates that prospective application of a 14-gene prognostic assay significantly predicts differences in disease-free survival. This prognostic information differs from NCCN high-risk clinicopathologic features and has clinical utility in better informing adjuvant chemotherapy recommendations.
