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Everett E Vokes
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MA 03 - Chemotherapy (ID 651)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Jin-Hyoung Kang, W. Su
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 502
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MA 03.09 - The Cost and the Benefit: Front-Line Immunotherapy for Non-Small Cell Lung Cancer (ID 9645)
12:00 - 12:05 | Author(s): Everett E Vokes
- Abstract
- Presentation
Background:
The U.S. Food and Drug Administration approved pembrolizumab in combination with carboplatin/pemetrexed for patients with untreated, metastatic, non-squamous, non-small cell lung cancer based on KEYNOTE 021G. This trial randomized 123 patients to carboplatin/pemetrexed versus carboplatin/pemetrexed/pembrolizumab with maintenance pembrolizumab. Maintenance pemetrexed was optional in both arms. Progression-free survival (PFS) was longer for carboplatin/pemetrexed/pembrolizumab (not reached vs. 8.9 months, HR 0.49, 95% CI 0.29-0.83, p=0.0035). No statistically significant improvement in overall survival (OS) has yet been demonstrated (HR 0.69, 95% CI 0.36-1.31, p=0.13), with neither arm reaching median OS. Frontline pembrolizumab improves PFS and OS in comparison to chemotherapy in patients with high PD-L1 expression. Drug cost information should be available to providers to better inform decision-making and assess value.
Method:
Dose calculations were based on the following: GFR 125, BSA 2.00 m2, carboplatin AUC 5, pemetrexed 500mg/m2, and pembrolizumab 200mg. Drug costs were obtained via the Centers for Medicare & Medicaid Services Pricing File.
Result:
Four cycles of carboplatin/pemetrexed/pembrolizumab followed by maintenance pembrolizumab and pemetrexed cost $618,889. Four cycles of carboplatin/pemetrexed followed by pemetrexed maintenance cost $249,972. Pembrolizumab alone for an equivalent number of cycles cost $368,917. Table 1: Regimen Cost Calculations Figure 1
Conclusion:
While the addition of pembrolizumab to front-line therapy resulted in an improvement in PFS in a phase II study of 123 patients, it increased medication costs 2.4 fold, from $249,972 to $618,889. Phase III trials are underway to more definitively assess the benefit of immunotherapy administered with chemotherapy in a broad population of patients. Treatment with carboplatin/pemetrexed/pembrolizumab cost 1.7 times that of pembrolizumab alone, and the addition of chemotherapy is of unclear benefit for patients with high PD-L1 expression. Further defining patient subsets who will benefit the most from this costly regimen should be undertaken. It is crucial healthcare professionals and patients understand the cost implications of front line therapy options.
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.07 - Veliparib in Combination with Paclitaxel/Carboplatin (P/C)-Based Chemoradiotherapy (CRT) in Patients with Stage III NSCLC (ID 10210)
16:25 - 16:30 | Author(s): Everett E Vokes
- Abstract
- Presentation
Background:
CRT is a standard for patients with Stage III non-small cell lung cancer (NSCLC). Veliparib (V) is a potent, orally bioavailable PARP1/2 inhibitor that can delay DNA repair following chemotherapy or radiation induced damage. A phase 2 study indicated favorable efficacy of V vs placebo when added to P/C in advanced NSCLC (Ramalingam et al. Clin Cancer Res. 2016). Based on these results, a phase 1/2 trial was initiated to study the safety and efficacy of V/P/C-based CRT in the treatment of Stage III NSCLC.
Method:
Patients without prior NSCLC therapy suitable for definitive CRT received V plus C AUC 2 + P 45 mg/m[2] weekly + 60 Gy over 6-9 weeks. V was escalated from 60 mg BID to a maximum planned dose based on prior studies of 240 mg BID via 3+3 design with over-enrollment allowed followed by consolidation therapy of V 120 mg BID + C AUC 6 + P 200 mg/m[2] for up to two 21-day cycles.
Result:
Thirty-nine patients (median age 66; 14 male) have been enrolled to date into dosing cohorts at 60 mg (7), 80 mg (9), 120 mg (7), 200 mg (8), and a maximum planned dose of 240 mg (8). Median tumor volume at screening was 81 cc (16-555 cc). PK of V was dose proportional. CRT or V required dose reduction for 0 or 1 patient, respectively. Four (10%) patients discontinued study during CRT. No DLTs were observed and an MTD has not been identified. The most common any-grade AEs were esophagitis (23), nausea (22), fatigue (20), neutropenia (19), and thrombocytopenia (19). 27 SAEs occurred including 12 SAEs with reasonable attribution to V but outside the DLT window including G3/4 febrile neutropenia (2), G3 dehydration (1), G3 vomiting (1), G3 esophagitis (1), G3 radiation esophagitis (1), G3 esophageal stricture (1), G3 intractable N/V (1), G3 aspiration pneumonia (1), G3 radiation pneumonitis (1), G4 sepsis (1), and G5 sepsis during consolidation (1). Of 29 patients evaluable for tumor assessment, best response was CR (2), PR (22), SD (3), and PD (2).
Conclusion:
V/P/C-based CRT followed by V/P/C consolidation therapy is a tolerable regimen for the treatment of Stage III NSCLC. The RPTD for V during CRT is 240mg BID. A randomized placebo-controlled phase 2 extension of this study is planned. Clinical trial information: NCT02412371
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MA 18 - Global Tobacco Control and Epidemiology II (ID 676)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 1
- Moderators:H. Kawai, Christian Klaus Manegold
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 511 + 512
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MA 18.06 - Clinical Prognostic Model for Older Patients with Advanced Non-Small Cell Lung Cancer (ID 8113)
16:20 - 16:25 | Author(s): Everett E Vokes
- Abstract
- Presentation
Background:
The median age at diagnosis of lung cancer is 70 years. Older patients are often not prescribed standard therapy. Due to multiple competing causes of death, older patients often do not demonstrate a benefit in overall survival (OS). It is important to know which older patients would actually be candidates for aggressive therapy based on their prognosis, and to develop a simple prognostic model that can help clinicians determine individual prognosis.
Method:
Data on patients enrolled on 38 NCI-sponsored cooperative group clinical trials of advanced non-small cell lung cancer (NSCLC) from 1991 to 2011 were analyzed. Multivariable Cox PH model was built with a stepwise procedure with all potential predictors: age, sex, race, ethnicity (Hispanic or non-Hispanic), performance status, initial stage, BMI, and weight loss in the past 3/6 months. We derived a prognostic score using the estimated Cox PH regression coefficient in the training set. To assess the performance of our prognostic model, we calculated the area under receiver operating characteristic (ROC) curve of 1- and 2-year survival in the testing set.
Result:
The final analysis included 1454 NSCLC patients ≥70 years of age. These patients were randomly divided into a training set (n=962) and a testing set (n=492). The prognostic risk score was calculated as: 3 (if male) + 3 (if PS=1) + 8 (if PS=2) + 11 (if initial stage=IV) + 4 (if weight loss). Patients were classified into three prognostic groups by tertiles: good (0-6), intermediate (7-14) and poor (≥15). The median OS in the three groups in the testing set were: 14.6 months (95% CI, 12.2-18.5); 12.2 months (95% CI, 10.7-14.4) and 7.0 months (95% CI, 5.6-8.9), respectively. Despite its simplicity, the present model had area under the 1-year and 2-year ROCs (0.63 and 0.68, respectively) that were higher than existing models.
Conclusion:
Male gender, poor performance status, distant metastases and weight loss immediately prior to diagnosis predict for poor OS in older patients with advanced NSCLC. This study proposes a simple prognostic model for older adults with advanced NSCLC based on basic clinical characteristics that are part of the routine evaluation process for every patient with NSCLC.
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MS 11 - Combined Modality Treatment for Superior Sulcus Tumors (ID 533)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:G.D. Castro, Philip Bonomi
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 503
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MS 11.05 - Definitive Chemoradiotherapy in Superior Sulcus Tumor (ID 7697)
12:00 - 12:15 | Presenting Author(s): Everett E Vokes
- Abstract
- Presentation
Abstract:
Superior sulcus tumors have been long defined as a distinct clinical entity. Symptoms including Horner’s syndrome and other neurologic findings as well as severe shoulder pain and SVC syndrome characterize this disease. Early on, the use of preoperative therapy was recognized as potentially useful. Over time, initial chemoradiotherapy followed by surgery has emerged as standard of care for patients with T3 or T4 lesions and N0 or N1 disease. 3-year survival rates of approximately 60% have been reported for surgically resectable patients with advanced disease. More recently, the addition of consolidation chemotherapy following subsequent surgery was evaluated, but its exact contributions to increasing survival remain unclear. The majority of patients will progress, usually with systemic disease and a large fraction of patients develop brain metastases. Patients with unresectable disease receive concurrent chemoradiotherapy as definitive therapy. Here, commonly used regimens such as the combination of cisplatin/etoposide, carboplatin/paclitaxel, and cisplatin/pemetrexed are utilized. However, more effective therapies are needed and special emphasis on increasing the systemic antitumor activity against micrometastatic disease will be required. The use of targeted therapies such as erlotinib or crizotinib for EGFR mutated or ALK fusion-related adenocarcinomas is currently under investigation. Of high recent interest is the possible addition of immune oncology agents such as the PD-1 or PD-L1 inhibitors. A recent report on the use of the PDL1 inhibitor durvalumab after completion of concurrent chemoradiotherapy in patients with unresectable stage IIIB disease has been reported as meeting its primary endpoint. It is likely that this and other studies will be relevant for superior sulcus tumors as well. Currently ongoing trials of increasing progression-free survival and their scientific basis will be reviewed.
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P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.04-003 - Phase II Trial of Atezolizumab Before and After Definitive Chemoradiation for Patients with Unresectable Stage III NSCLC (ID 9662)
09:30 - 09:30 | Author(s): Everett E Vokes
- Abstract
Background:
More than 40,000 US patients per year present with stage III NSCLC. These patients are of particular interest in that most are not resectable and while they can be treated with curative intent with excellent initial responses, only approximately 25% will be cured by conventional chemoradiotherapy. This, together with the generally better health of this cohort compared to patients with metastatic NSCLC, makes these patients ideal candidates for studies of immunotherapy to increase cure rates. The combination of checkpoint inhibition to counter tumor related immunosuppression along with standard chemoradiotherapy that depletes T-regulatory cells should create immunologic “space” to facilitate clonal expansion of effector T-cells in an environment that fosters improved tumor immunogenicity by blocking PD-L1. Responses to immunotherapy seem to be higher in patients for whom significant cytoreduction can be achieved, such as with radiation of all known disease. Further, both chemotherapy and radiation may expose otherwise hidden antigens that can present additional targets to the reconstituting immune system.
Method:
This phase II single arm Alliance Foundation study (NCT03102242) will evaluate safety and efficacy of atezolizumab before and after definitive chemoradiotherapy. 63 patients with stage III NSCLC, PS 0-1, no active autoimmune disease, adequate cardiopulmonary function and no underlying organ dysfunction will be enrolled at 15 Alliance sites in the US. Treatment consists of 4 cycles of neoadjuvant atezolizumab 1200 mg IV q 21 days before chemoradiotherapy with restaging after cycles 2 and 4. Nonprogressing patients undergo weekly carboplatin and paclitaxel concurrent with 60 Gy thoracic radiotherapy followed by 2 cycles of carboplatin and paclitaxel consolidation followed by completion of one year of atezolizumab. The primary endpoint of this pilot study is disease control (CR+PR+SD) after neoadjuvant atezolizumab. Secondary endpoints include ORR, PFS and OS, safety and QoL assessed by the EORTC QLQ-30. Translational endpoints seek to define the role of PD-L1 biomarker testing in selecting the population most likely to respond to neoadjuvant and adjuvant immunotherapy together with standard chemoradiotherapy and to study the association of biomarkers, including immunologic signatures, with response and survival. Tumor tissue will be assessed at study entry and, where possible, at progression. Plasma and immune cells will be assessed at baseline, post neoadjuvant atezolizumab, post chemoradiotherapy, during adjuvant atezolizumab and at study completion or progression. Analyses may include multipanel immunohistochemistry, gene expression profiling, whole exome and T cell receptor sequencing, cytokine/chemokine analysis, flow cytometry immunophenotyping, and T cell function.
Result:
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Conclusion:
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