Virtual Library
Start Your Search
R. Lilenbaum
Author of
-
+
MTE27 - Treatment of Lung Cancer Patients with Poor Performance Status (Ticketed Session) (ID 320)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 07:30 - 08:30, Lehar 1-2
-
+
MTE27.01 - Treatment of Lung Cancer Patients with Poor Performance Status (ID 6588)
07:30 - 08:30 | Author(s): R. Lilenbaum
- Abstract
- Presentation
Abstract:
Performance status (PS) captures a patient’s ability to perform daily activities and provides a measure of impairment as a function of tumor burden. The Eastern Cooperative Oncology Group (ECOG) scale is the most frequently used and ranges from 0 (fully ambulatory without symptoms) to 5 (dead). Typically, patients with an ECOG PS of 0 and 1 are labeled as “good PS”, are typically treated with combination regimens, and are the focus of the majority of the clinical trials. Patients with “poor PS”, mostly ECOG 2, but also 3 and occasionally 4, have been largely excluded from clinical trials. Patients with a PS of 2 account for approximately 30-40% of patients diagnosed with advanced non-small cell lung cancer (NSCLC) in clinical practice (1). As a result of the lack of dedicated research, current guidelines are equivocal with respect to the optimal therapy for these patients and their management remains inconsistent, ranging from best supportive care to combination chemotherapy. Cooperative group studies in the 1980’s and 1990’s suggested that poor PS patients (ECOG ≥2) derived little or no benefit from systemic chemotherapy and had high rates of treatment-related morbidity and mortality (2). This perspective permeated clinical research and clinical practice for over 2 decades. While concerns about safety and benefit remain appropriate, the advent of better supportive care, along with more effective and tolerable carboplatin-based doublets have led to new trials in this subset of patients. Two large phase III randomized trials in PS 2 patients in the mid-2000’s provide insights into this heterogeneous cohort. In one trial, 400 patients were assigned to standard carboplatin plus paclitaxel or carboplatin plus another formulation of paclitaxel (3). In the other trial, 400 patients were assigned to single agent gemcitabine or vinorelbine (4). The identical eligibility criteria led to a separate publication comparing single agent vs. combination chemotherapy (5). The response rate (38 versus 16 percent) and the median time to progression (4.6 versus 3.5 months) were statistically superior with combination chemotherapy. Overall survival trended in the same direction, but the difference was not significant (8.0 versus 6.6 months). Toxicity, as expected, was higher with combination chemotherapy. The question of single agent vs combination chemotherapy was addressed in a definitive manner by a phase III randomized trial that compared pemetrexed alone or in combination with carboplatin in 205 eligible patients with PS 2 (6). Respectively, the response rates were 10% vs 24%; the median progression free survival was 2.8 vs. 5.8 months; and the median survival was 5.3 vs. 9.3 months, all statistically significant in favor of the combination regimen. Toxicity was manageable but 4 treatment-related deaths were observed in the combination arm. This trial has set a new standard for treatment of advanced NSCLC patients with a PS of 2. The advent of targeted agents led to the exploration of these agents as a “gentler approach” to PS 2 patients, irrespective of the presence or absence of the mutation. In a phase II randomized trial, patients were assigned to either erlotinib or a combination of carboplatin and paclitaxel (7). Patients treated with erlotinib had a significantly shorter median survival compared to chemotherapy (6.5 vs 9.7 months, HR 1.73, 95% CI 1.09-2.73). As shown in other trials, EGFR inhibitors should not be given to untreated patients without the mutation, regardless of the PS. Guidelines from the American Society of Clinical Oncology (ASCO) state that the data for patients with PS 2 are insufficient to make a strong recommendation for combination chemotherapy, and single agent therapy may be appropriate if the perception of risk outweighs the perception of benefits (8). The European Society of Medical Oncology (ESMO), after reviewing the same body of data, came up with a straightforward recommendation for carboplatin-based combinations to all eligible PS 2 patients (9). The National Comprehensive Cancer Network (NCCN) merged PS 2 patients into the PS 0-1 group for recommendations regarding first line therapy, with no obvious distinction between the subsets (10). This progressive approach recognizes the advances made in the management of PS 2 patients in the past decade and extends the benefits of systemic therapy to a large group of patients who were, until recently, offered inferior treatments. References: Lilenbaum RC, Cashy J, Hensing TA, et al. Prevalence of poor performance status in lung cancer patients: implications for research. J Thorac Oncol 2008; 3:125 Sweeney CJ, Zhu J, Sandler AB, et al. Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II trial in patients with metastatic nonsmall cell lung carcinoma . Cancer 2001; 92:2639 Langer CJ, O'Byrne KJ, Socinski MA, et al. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol 2008; 3:623 O'Brien ME, Socinski MA, Popovich AY, et al. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol 2008; 3:728 Lilenbaum R, Villaflor VM, Langer C, et al. Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2: prognostic factors and treatment selection based on two large randomized clinical trials. J Thorac Oncol 2009; 4:869 Zukin M, Barrios CH, Pereira JR, et al. Randomized Phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small cell lung cancer and Eastern Coopertaive Group performance status of 2. J Clin Oncol 2013; 31:2849–2853 Lilenbaum R, Axerold R, Thomas S, et al. Randomized Phase II Trial of Erlotinib or Standard Chemotherapy in patients with Advanced Non-Small Cell Lung Cancer and a Performance Status of 2. J Clin Oncol 2008; 26:863-869 Masters GA, Temin S, Azzoli G, et al. Systemic therapy for stage IV non-small cell lung cancer: American society of clinical oncology clinical practice guideline update. J Clin Oncol 2015; 62:1342 Reck M, Popat S, Reinmuth N, et al. Metastatic non-small cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol 2014; 25 (suppl 3): iii27 National Comprehensive Cancer Network. Non-Small Cell Lung cancer (Version 4.2016). http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. Accessed September 15, 2016
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.
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-052 - Afatinib with or without Cetuximab for First-Line Treatment of EGFR-Mutant NSCLC: Interim Safety Results of SWOG S1403 (ID 5798)
14:30 - 15:45 | Author(s): R. Lilenbaum
- Abstract
Background:
Afatinib is used as first-line therapy for EGFR-mutant non-small cell lung cancer (NSCLC), however resistance invariably develops. To attempt to delay resistance and improve survival, we are conducting a randomized Phase II/III trial of afatinib plus cetuximab versus afatinib alone in treatment-naïve patients with advanced EGFR-mutant NSCLC (NCT02438722).
Methods:
Previously untreated patients with EGFR exon 19 deletion or L858R point mutation are randomized to afatinib 40mg PO daily plus cetuximab 500mg/m2 IV every 2 weeks (afat/cetux) or afatinib 40mg PO daily (afat). Dose reductions are performed for grade 3-4 or intolerable or medically concerning grade 2 adverse events (AEs) per CTCAE v4.0. The Phase II primary endpoint is progression-free survival and the Phase III primary endpoint is overall survival. Here we review the safety data after enrollment of the first 53 patients.
Results:
53 patients were registered as of June 30, 2016, and safety has been assessed in 47 (23 treated with afat/cetux and 24 with afat, see Table). Grade 1-2 rash occurred in 71% of patients receiving afat/cetux and 63% of patients on afat. Grade 3 rash was noted in 22% of patients on afat/cetux. Fatigue was more common in the combination arm; all occurrences were grade 1-2. Grade 1-2 diarrhea and other gastrointestinal AEs were comparable between the two arms. There were similar numbers of dose reductions for AEs on each arm. Three patients discontinued treatment due to AEs: 2 on the afat/cetux arm due to hyperglycemia and accumulated side effects and 1 on the afat arm due to weight loss and diarrhea. Figure 1
Conclusion:
In this randomized trial of afat/cetux versus afat, treatment was tolerable in both arms of the study. Skin toxicity appears to be worse with the combination however other AEs are similar between the two groups. Enrollment to this trial is ongoing.
-
+
P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02c-048 - A Phase I/II Trial Evaluating the Combination of Stereotactic Body Radiotherapy and Pembrolizumab in Metastatic NSCLC (ID 5249)
14:30 - 15:45 | Author(s): R. Lilenbaum
- Abstract
Background:
Immune checkpoint inhibitors are taking on a growing role in the treatment of patients with metastatic NSCLC. Pre-clinical evidence suggests that radiotherapy may increase the frequency, or enhance the strength of the host anti-cancer immune response. We report the preliminary results of an ongoing phase I/II trial combining stereotactic body radiotherapy (SBRT) and the anti-PD-1 antibody pembrolizumab in patients with metastatic NSCLC.
Methods:
Eligible patients are those with metastatic NSCLC who have received no prior immune-directed therapy, and have at least 2 sites of measurable disease as per RECIST 1.1. PD-L1 expression is not required for study entry. All patients are treated with pembrolizumab at 200 mg every 3 weeks until development of progressive disease by immune-related RECIST criteria (irPD). After irPD, patients receive SBRT to a single site of disease and continue pembrolizumab. The primary endpoint is safety and tolerability. Secondary endpoints include the pre- and post-SBRT overall response rate.
Results:
27 patients with advanced NSCLC have enrolled and started trial therapy. The overall response rate (irPR and irCR) to the initial course of pembrolizumab is 35%. To date, 13 patients have had irPD: 5 were not eligible for SBRT and stopped study treatment (2 developed new brain metastases, 3 had decline in PS), and 8 patients received SBRT to a single site of disease (6 thoracic, 1 adrenal, 1 vertebral) and continued pembrolizumab. 5 of these patients are evaluable for post-SBRT response: 1 patient had confirmed irPD, 4 have irSD and continue pembrolizumab post-SBRT at a median duration of 3 months (range 1 to 5 months). 2 of the 4 patients with irSD have had > 20% decrease in the sum of diameters of their unirradiated targets, since SBRT. Regarding adverse events, in the pre-SBRT phase 6 of 27 patients (22%) developed grade 3 treatment-related toxicity (2 colitis, hepatitis, pneumonitis, hypothyroidism, conjunctivitis). In the SBRT and post-SBRT phases, there have been no grade 2 or greater treatment-related events.
Conclusion:
The addition of SBRT to pembrolizumab has not resulted in an increase in treatment-related toxicity. Several patients who had serially confirmed irPD to pembrolizumab monotherapy underwent SBRT and now have irSD, with some evidence of tumor regression. Updated results will be presented.
