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R. Govindan



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    MS 16 - Novel SCLC Therapies (ID 34)

    • Event: WCLC 2015
    • Type: Mini Symposium
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      MS16.06 - New Chemotherapies (Eribulin, Aldoxorubicin, Etirinotecan, MM398) (ID 1921)

      14:15 - 15:45  |  Author(s): R. Govindan

      • Abstract
      • Presentation

      Abstract:
      Small cell lung cancer (SCLC) accounts for nearly 15% of newly diagnosed lung cancers.[1] With the advent of tyrosine kinase inhibitors, the last decade has witnessed remarkable improvements in the outcomes of patients with non-small cell lung cancer (NSCLC). However, outcomes in patients with SCLC continue to remain dismal. Currently approved targeted therapies have minimal role in the management of SCLC, since unlike NSCLC, targetable tyrosine kinase alterations are rarely witnessed in SCLC.[2,3] Cytotoxic chemotherapy has therefore continued to remain the standard of care for SCLC. SCLC is usually very sensitive to first-line platinum based therapies.[4] Nevertheless, these responses are seldom durable and majority of patients relapse within weeks to months of treatment completion. Relapsed SCLC is a tough disease to treat and barely responds to conventional therapies. There is hence is an urgent need to develop novel therapeutic strategies that are capable of improving survival in patients with SCLC - particularly those with relapsed disease. Several new chemotherapeutic agents are currently being developed and actively studied in various solid tumors. The objective of this article is to highlight some of these newer chemotherapies and discuss their potential relevance in the management of SCLC. Eribulin mesylate is a non-taxane halichondrin B analogue derived from the marine sponge Halichondria okadaic.[5] Eribulin sequesters tubulin and inhibits mitotic spindle formation, leading to cell cycle arrest in G2-M and eventually cell death. Eribulin is currently FDA approved in the United States for the management of metastatic breast cancer in patients receiving prior treatment with at least two chemotherapy regimens, including an anthracycline and a taxane. In the phase III EMBRACE trial, as a part of which 762 women with breast cancer were randomized to receive eribulin or chemotherapy of the treating physician’s choice, overall survival (OS) was significantly improved with eribulin (13.1 vs. 10.6 months, HR 0.81 p=0.041).[6] Eribulin as single agent and in combination with erlotinib were shown to be active and well tolerated in patients with NSCLC treated with prior platinum based therapies.[7] In the study by Spira and colleauges, eribulin was dosed at 1.4mg/m2 on days 1 and 8 of a 21 day cycle (similar to breast cancer dosing schedule) and in a second cohort of patients at 1.4 mg/m2 on days 1, 8 and 15 of a 28 day schedule.[8] Among these, the 21 day dosing schedule was shown to be better tolerated and active with a median OS of 9.4 months in the second line setting for NSCLC. However, when used in combination with a second agent, the maximum tolerated dose (MTD) of eribulin was much lower. In a phase Ib/II study involving pretreated NSCLC patients, the MTD of eribulin was 0.9mg/m2, with 500mg/m2 of pemetrexed, administered on day 1 of a 21 day cycle.[9] Unfortunately, the combination was tolerable but showed no therapeutic benefit at this dose. Aldoxorubicin, formerly known as INNO-206, combines a molecular linker that allows doxorubicin to bind covalently to serum albumin upon intravenous administration.[10] This formulation releases doxorubicin in the acidic tumor microenvironment. Aldoxorubicin is currently being actively investigated in the management of soft-tissue sarcomas and glioblastoma. In a phase Ib/II study by Chawla and colleagues, the MTD of aldoxorubicin was 350mg/m2 administered every 21 days.[11] The drug showed a partial response rate of 20% and stable disease rate of 40% in 25 patients with advanced chemotherapy refractory cancers, among which most patients (68%) had soft tissue sarcomas. Aldoxorubicin was considered to be safe and efficacious in these patients. Currently, aldoxorubicin is being studied as part of an ongoing randomized phase IIb trial in patients with relapsed/refractory SCLC (NCT02200757). This study will compare progression free survival (PFS) between patients receiving aldoxorubicin at a dose of 230mg/m2 every 21 days, with those receiving topotecan. Irinotecan is a chemotherapeutic agent known to be active in SCLC. SN38 is the active metabolite of irinotecan, which through its inhibitory action on DNA topoisomerase I induces DNA breaks and inhibits repair. Etirinotecan pegol is a formulation designed to provide prolonged systemic exposure to SN38.[12] In a phase I dose escalation study, 66 patients received etirinotecan on three different dosing schedules and 115mg/m2 administered on days 1, 8 and 15 of 21 day cycles was established as the MTD. Diarrhea was observed in 5 patients at the 115mg/m2 dose level, with one patient experiencing grade 3 or higher diarrhea. The cholinergic diarrhea that is seen with irinotecan was not observed with etirinotecan. The drug was also shown to induce partial responses in patients with various cancers including SCLC. Etirinotecan was also recently reported to be active in heavily pretreated ovarian cancer patients.[13] In this study etirinotecan was administered at 145mg/m2 every 14 or 21 days, and the 21 day dosing schedule was found to be better tolerated and selected for further study. A phase II study that plans to study the effect of etirinotecan dosed every 21 days on PFS in patients with relapsed SCLC is currently recruiting (NCT01876446). Another formulation of irinotecan, MM-398, which is a nanoliposomal encapsulated formulation that packs nearly 80,000 irinotecan molecules in a 100nm liposome, is also being actively investigated in pancreatic, gastrointestinal, and other solid tumors.[14] Results from the NAPOLI-1 trial, a phase III study in which patients with metastatic pancreatic cancer who were previously treated with gemcitabine, were randomized to receive either single agent MM-398 at 120mg/m2 every 3 weeks or a combination of 5-fluorouracil (5FU), leucovorin (LV) and MM-398 at 80mg/m2, or 5-FU/LV alone, were recently presented.[15] The primary objective of this study was OS and in the intention to treat analysis, this was significantly improved in the MM-398/5FU/LV combination arm compared to the 5FU/LV arm (median OS 6.1 months vs. 4.2 months, HR-0.57, p=0.0009). Although there is currently no clinical data regarding the efficacy or safety of these newer drugs in patients with SCLC, considering that taxanes, anthracyclines, and DNA topoisomerase inhibitors are each individually active in SCLC, and that newer agents such as these have shown some positive preliminary results in other cancers - there is hope and optimism that over the next few years we will witness substantial progress in the management of SCLC. Overall, the need for developing and implementing well-designed biomarker driven clinical studies to investigate the role of these and other novel agents in SCLC is now greater than ever. References 1. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24:4539-44. 2. Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 2012;44:1111-6. 3. Peifer M, Fernández-Cuesta L, Sos ML, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 2012;44:1104-10. 4. Kalemkerian GP, Akerley W, Bogner P, et al. Small cell lung cancer. J Natl Compr Canc Netw 2013;11:78-98. 5. Scarpace SL. Eribulin mesylate (E7389): review of efficacy and tolerability in breast, pancreatic, head and neck, and non-small cell lung cancer. Clin Ther 2012;34:1467-73. 6. Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011;377:914-23. 7. Mok TS, Geater SL, Iannotti N, et al. Randomized phase II study of two intercalated combinations of eribulin mesylate and erlotinib in patients with previously treated advanced non-small-cell lung cancer. Ann Oncol 2014;25:1578-84. 8. Spira AI, Iannotti NO, Savin MA, et al. A phase II study of eribulin mesylate (E7389) in patients with advanced, previously treated non-small-cell lung cancer. Clin Lung Cancer 2012;13:31-8. 9. Waller CF, Vynnychenko I, Bondarenko I, et al. An open-label, multicenter, randomized phase Ib/II study of eribulin mesylate administered in combination with pemetrexed versus pemetrexed alone as second-line therapy in patients with advanced nonsquamous non-small-cell lung cancer. Clin Lung Cancer 2015;16:92-9. 10. Kratz F. A clinical update of using albumin as a drug vehicle - a commentary. J Control Release 2014;190:331-6. 11. Chawla SP, Chua VS, Hendifar AF, et al. A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma. Cancer 2015;121:570-9. 12. Jameson GS, Hamm JT, Weiss GJ, et al. A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Clin Cancer Res 2013;19:268-78. 13. Vergote IB, Garcia A, Micha J, et al. Randomized multicenter phase II trial comparing two schedules of etirinotecan pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer. J Clin Oncol 2013;31:4060-6. 14. Saif MW. MM-398 achieves primary endpoint of overall survival in phase III study in patients with gemcitabine refractory metastatic pancreatic cancer. JOP 2014;15:278-9. 15. Dhindsa N, Bayever E, Li C, et al. NAPOLI-1: randomized phase 3 study of MM-398 (nal-iri), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer progressed on or following gemcitabine-based therapy. Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193.

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    ORAL 06 - Next Generation Sequencing and Testing Implications (ID 90)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL06.04 - Discussant for ORAL06.01, ORAL06.02, ORAL06.03 (ID 3302)

      10:45 - 12:15  |  Author(s): R. Govindan

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    ORAL 10 - SCLC (ID 98)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      ORAL10.01 - A DLL3-Targeted ADC, Rovalpituzumab Tesirine, Demonstrates Substantial Activity in a Phase I Study in Relapsed and Refractory SCLC (ID 1598)

      10:45 - 12:15  |  Author(s): R. Govindan

      • Abstract
      • Slides

      Background:
      Rovalpituzumab tesirine (i.e. SC16LD6.5) is a Delta-like protein 3 (DLL3) targeted antibody-drug conjugate (ADC) comprised of a humanized monoclonal antibody, dipeptide linker, and pyrrolobenzodiazepine (PBD) dimer toxin with a drug-to-antibody ratio of 2. DLL3 is highly expressed in human neuroendocrine tumors and their tumor-initiating cells, including approximately two-thirds of small cell lung cancer (SCLC). DLL3 is not expressed at detectable levels in normal tissues. Rovalpituzumab tesirine induced tumor regression and prolonged time to progression significantly outperforming cisplatin/etoposide in DLL3-expressing SCLC patient-derived xenograft tumor models. Based on this promising activity, a first-in-human phase I trial in patients (pts) with recurrent SCLC was initiated and preliminary results are reported below.

      Methods:
      SCLC pts with progressive disease after 1 or 2 previous lines of therapy received escalating doses of rovalpituzumab tesirine as a single agent once every 3 weeks (Q3W) in 1-3 pt cohorts until dose limiting toxicities (DLTs) were observed. The doses were 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg Q3W. Midway through accrual, pharmacokinetic data revealed a longer than expected ADC half-life of ~11 days, prompting evaluation of a Q6W schedule. A DLL3 antibody was developed and utilized to assess antigen expression in archived tumor specimens. Biomarker positive (BM+) tumors were defined by IHC membrane-associated H-Scores ≥ 120.

      Results:
      52 pts were treated: 34 Q3W and 18 Q6W; 24F/28M; median age, 61 years (44-82). Acute and chronic DLTs of thrombocytopenia and capillary leak syndrome (CLS) were observed at 0.8 and 0.4 mg/kg Q3W, respectively. Maximum tolerated doses (MTD) of 0.2 mg/kg Q3Wx3 cycles and 0.3 mg/kg Q6Wx2 cycles were further evaluated in expansion cohorts. The most common treatment emergent adverse events of any grade among all pts were fatigue (40%), rash (39%), nausea (29%), dyspnea (23%), decreased appetite (21%) and vomiting (21%). Grade 3+ CLS and thrombocytopenia were seen in 7 (14%) and 3 (6%) pts, respectively, with no reported Grade 5 toxicity. Of 38 archived tumor specimens received from enrolled pts, 23 (61%) were DLL3 BM+. Among the 16 confirmed DLL3 BM+ pts treated at the MTDs, 7 pts (44%) had partial response (PR) and 8 pts (50%) achieved stable disease (SD) for a combined clinical benefit rate (CBR) of 94%. In all evaluable pts treated at the MTD without regard for DLL3 biomarker status (n=32), the ORR was 22% (n=7 PR) and SD 53% (n=17), for a CBR of 75%. Notably, all pts with PRs that were treated at the MTD, and those having the most durable clinical benefit (up to 569 days OS), were BM+. Similar response rates were observed among pts sensitive and refractory to first-line therapy, and in the third-line setting where no standard-of-care currently exists.

      Conclusion:
      Rovalpituzumab tesirine, a first-in-class DLL3-targeted ADC, has manageable toxicity and demonstrated significant anti-tumor activity (44% ORR and 95% CBR) as a single agent in second- and third-line pts with recurrent DLL3 BM+ SCLC. A pivotal study is being planned.

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    ORAL 20 - Chemoradiotherapy (ID 124)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      ORAL20.02 - Safety Results of the Consolidation Phase of a Phase III (PROCLAIM): Pemetrexed, Cisplatin or Etoposide, Cisplatin plus Thoracic Radiation Therapy followed by Consolidation Cytotoxic Chemotherapy in Locally Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 645)

      10:45 - 12:15  |  Author(s): R. Govindan

      • Abstract
      • Presentation
      • Slides

      Background:
      Standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many patients die from recurrent disease, indicating that new treatment strategies are needed.

      Methods:
      PROCLAIM is a phase III trial comparing overall survival in patients with unresectable stage III nonsquamous NSCLC receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation (Arm A) versus etoposide+cisplatin (EtoCis) and concurrent radiotherapy for 2 cycles followed by consolidation with a platinum-based doublet of choice for up to 2 cycles (Arm B). Possible consolidation therapies in Arm B were EtoCis, vinorelbine+cisplatin (VinCis), and paclitaxel+carboplatin (PacCarb). Overall efficacy and safety results for the intent-to-treat population will be presented in a separate disclosure. Safety was a secondary objective. Interim safety results for the concurrent phase were previously presented. Here we present safety results for the consolidation phase. Treatment-emergent adverse events (TEAEs) were assessed according to the Common Terminology Criteria for Adverse Events (v3.0, CTCAE). TEAE incidences were compared using Fisher’s exact test (two-sided α=0.05).

      Results:
      Of 598 randomized patients, 555 were treated in the concurrent phase (Arm A: N=283; Arm B: N=272), most of whom (Arm A: n=229 [80.9%]; Arm B: n=202 [74.3%]) continued on to the consolidation phase (Arm B patients: EtoCis [33.5%], PacCarb [26.8%], VinCis [14.0%]). Baseline characteristics, including age, gender, performance status, smoking status, stage, and origin, were well-balanced across arms. Percentages of patients in Arm A completing ≥2, ≥3, and 4 consolidation cycles were 95.2%, 84.3%, and 73.4%, respectively. Percentages of patients in Arm B completing 2 consolidation cycles (maximum) were EtoCis (89.0%), PacCarb (93.2%), and VinCis (86.8%). Mean dose intensities for pemetrexed, etoposide, vinorelbine, cisplatin, paclitaxel, and carboplatin were 95.4%, 94.0%, 84.2%, 91.2%, 88.7%, and 92.7%, respectively. More patients in Arm B, compared to Arm A, experienced dose reductions, dose omissions, and cycle delays. Patients in Arm B reported more grade 3/4/5 drug-related TEAEs than Arm A (51.0% versus 31.0%, p<0.001; Table). Rates of drug-related serious AEs were similar between groups (Arm A: 14.4%; Arm B: 13.4%).

      Drug-related Grade 3/4/5 TEAEs Occurring in ≥2% of Patients (or of Clinical Relevance) in the Consolidation Phase
      CTCAE Arm A (N=229) n (%) Arm B (N=202) n (%)
      Neutrophils 27 (11.8) 76 (37.6)*
      Leukocytes 19 (8.3) 29 (14.4)
      Hemoglobin 6 (2.6) 9 (4.5)
      Platelets 5 (2.2) 10 (5.0)
      Febrile neutropenia 7 (3.1) 7 (3.5)
      Lymphopenia 8 (3.5) 5 (2.5)
      Pneumonitis/pulmonary infiltrates 5 (2.2) 2 (1.0)
      Fatigue 2 (0.9) 4 (2.0)
      Pneumonia 5 (2.2) 0
      Esophagitis 0 3 (1.5)
      *p<0.001, Fisher’s exact test. Note: Of the TEAEs listed here, only one case (0.4%, Arm A, pneumonia) was grade 5.


      Conclusion:
      During the PROCLAIM consolidation phase, most patients were able to complete the planned number of cycles in either arm, with the highest dose intensity corresponding to pemetrexed. Pemetrexed consolidation had a significantly lower incidence of drug-related grade 3/4/5 TEAEs than the platinum doublets in Arm B. A more detailed analysis of Arm B (by treatment regimen) is underway.

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    ORAL 33 - ALK (ID 145)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL33.05 - Pooled Analysis of CNS Response to Alectinib in Two Studies of Pre-Treated ALK+ NSCLC (ID 1219)

      16:45 - 18:15  |  Author(s): R. Govindan

      • Abstract
      • Presentation
      • Slides

      Background:
      The central nervous system (CNS) is a frequent site of progression in ALK+ NSCLC patients treated with crizotinib, thus good CNS efficacy is of crucial importance for new ALK inhibitors. Two recent phase II studies examined the efficacy and safety of alectinib in patients with ALK+ NSCLC who progressed after crizotinib; data from both studies were pooled to further examine the efficacy of alectinib in the CNS.

      Methods:
      Both phase II, single-arm, multicenter studies enrolled ALK+ NSCLC patients previously treated with crizotinib. One study was conducted in North America only (NP28761; NCT01871805), the other was global (NP28673; NCT01801111). All patients received 600mg oral alectinib twice daily. A primary endpoint of both studies was objective response rate (ORR) by independent review committee (IRC) and key secondary endpoints included CNS ORR by IRC and CNS duration of response (DOR). Response was determined according to RECIST v1.1. All patients underwent imaging at baseline to assess CNS metastases.

      Results:
      The pooled analysis population comprised 225 patients (n=87 from NP28761 and n=138 from NP28673); baseline characteristics were similar to each study population, with most patients being non-smokers, <65 years old with ECOG performance status 0/1. Median follow-up was 27.7 weeks. Fifty patients had measurable CNS disease at baseline (MD) while a further 85 had non-measurable disease (NMD) at baseline; both groups together (M+NMD) comprised 135 patients, 60% of the overall study population. In the MD group, 34 patients (68%) had received prior radiotherapy, but 24 of them had completed that radiotherapy >6 months prior to starting alectinib. For the M+NMD group, 94 patients (70%) had received prior radiotherapy, with 55 completing this >6 months prior to starting alectinib. In the MD group, 30/50 patients had a CNS response (60.0%; 95% CI 45.2–73.6%), with 7 complete responses (CR; 14.0%) and a CNS DCR of 90.0% (78.2–96.7%). In the M+NMD group, 22 additional patients had a CR (29/135; 21.5%), giving a CNS ORR of 38.5% (30.3–47.3%), with a CNS DCR of 85.2% (78.1–90.7%). Complete responses were seen in patients with and without prior radiotherapy. Median CNS DOR after only 17% of events in both groups was 7.6 months (5.8–7.6) in the MD group (n=30) and 7.6 months (5.8–10.3) in the M+NMD group (n=52), which is similar to the systemic DOR reported in both studies (Ou et al, ASCO 2015; Gandhi et al, ASCO 2015). Tolerability was also similar to the overall study population.

      Conclusion:
      Alectinib showed promising efficacy in the CNS in ALK+ NSCLC patients previously treated with crizotinib, achieving a complete response rate of 22% and a DCR of 85%, irrespective of prior radiotherapy. The CNS response was sustained for an equivalent duration to the systemic response, suggesting that alectinib could provide an effective treatment for patients with ALK+ NSCLC while actively targeting CNS metastases. The ongoing phase III clinical studies will assess the systemic and CNS efficacy of alectinib versus crizotinib as front-line therapy for ALK+ NSCLC patients.

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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
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      P2.01-004 - Oncologists' Comprehension and Beliefs Surrounding Cancer Immunotherapy in Advanced NSCLC (ID 1267)

      09:30 - 17:00  |  Author(s): R. Govindan

      • Abstract
      • Slides

      Background:
      Advanced NSCLC is now recognized as an immune-modifiable disease, and with the approval of the first PD-1 inhibitor, immune checkpoint inhibitors represent a new standard of care for patients with previously treated squamous cell lung cancer. The objective of this study was to evaluate oncologists’ familiarity with cancer immunotherapy in the context of advanced NSCLC and the impact of an educational curriculum on narrowing gaps in clinical practices.

      Methods:
      An expert panel of oncologists identified educational gaps in the area of cancer immunotherapy. A series of 9 CME online activities were developed, 2 of which centered on advanced NSCLC and are the focus of this study. Interactivity questions allowed learners to self-report their familiarity with immunotherapy concepts in the management of advanced NSCLC, while case vignette and knowledge-based questions were constructed around evidence-based medicine. Confidentiality of survey respondents was maintained and responses were de-identified and aggregated prior to all analyses.

      Results:
      1368 oncologists participated in the 2 activities on advanced NSCLC. As seen in the table below participation in the education activities resulted in numerous improvements in knowledge and competence as seen in the table below. Despite improvements, several important gaps remained. Only70% of oncologists comprehend that a tumor may increase in size or new lesions appear during initial therapy with an immune checkpoint inhibitor. In addition, about half of oncologists still had difficulty grasping how immune checkpoints downregulate T cell responses. Finally, oncologists still had difficulty identifying the unique side effect profile associated with immune checkpoint inhibitors. In addition, 55% of oncologists reported they were not comfortable with managing side effects associated with these agents.

      Table
      % answered correctly % answered correctly
      Pre-Activity Post-Activity
      Comprehension of Basic Immunology
      Interaction of TCR with MHC-peptide complex and co-stimulatory receptors CD28/CD80 and CD86 52% 69%
      Which does not represent a role of an immune checkpoint in the adaptive immune response: CTLA-4 binds to CD28, augmenting T-cell activation 50% 57%
      Knowledge of Immune System’s Role in Response to Cancer
      T cell infiltration and decreased risk of recurrence 69% 76%
      Disease progression on an immune checkpoint inhibitor 65% 71%
      Efficacy, Safety, Limitations of Immune Checkpoint Inhibitors
      Limitations PD-L1 as a biomarker 26% 70%
      Durability of response 5% 30%
      Unique side effect profile 41% 59%


      Conclusion:
      The study evaluated oncologists’ familiarity with cancer immunotherapy in advanced NSCLC and demonstrated the necessity of developing targeted educational interventions for improving the knowledge and practice patterns of oncologists. Additional education is needed to continue to improve clinicians’ competence in the use of cancer immunotherapies in the management of NSCLC.

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    P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P3.01-089 - Nab-Paclitaxel with or without CC-486 as Second-Line Therapy for NSCLC (ABOUND.2L) (ID 719)

      09:30 - 17:00  |  Author(s): R. Govindan

      • Abstract
      • Slides

      Background:
      Many patients with advanced non-small cell lung cancer (NSCLC) will experience disease progression during first-line chemotherapy. Effective and well-tolerated second-line treatment options for this patient population are limited. In a multicenter phase III trial, first-line treatment with nab-paclitaxel plus carboplatin (nab-P/C) significantly improved the primary endpoint of overall response rate (ORR) compared with solvent-based paclitaxel plus C in patients with advanced NSCLC (33% vs 25%; P = 0.005; Socinski et al. J Clin Oncol. 2012;30:2055-2062). nab-P combined with CC-486, an oral formulation of azacitidine, resulted in promising outcomes in a phase I trial of patients with relapsed/refractory solid tumors (LoRusso et al. Mol Cancer Ther. 2013;12(11 Suppl):Abstract A120). In the open-label, multicenter phase II ABOUND.2L trial, the safety and efficacy of nab-P with or without CC-486 will be evaluated in the second-line treatment of patients with advanced nonsquamous NSCLC.

      Methods:
      Approximately 160 patients who have received 1 platinum-containing chemotherapy regimen for treatment of advanced disease will be randomized 1:1 to CC-486 200 mg/day on days 1 to 14 every 21 days plus nab-P 100 mg/m[2] intravenously (IV; 30-minute infusion) on days 8 and 15 every 21 days or nab-P 100 mg/m[2] IV (30-minute infusion) on days 1 and 8 every 21 days. Key eligibility criteria include histologically or cytologically confirmed advanced nonsquamous NSCLC, ECOG performance status ≤ 1, adequate organ function, no active brain metastases, no prior taxane therapy, no known EGFR mutation or EML4-ALK translocation, and peripheral neuropathy grade < 2. Randomization will be stratified by ECOG performance status (0 vs 1), sex, and smoking status (yes vs no). ClinicalTrials.gov identifier NCT02250326.

      Key Endpoints
      Primary -Progression-free Survival
      Secondary -Disease control rate -Overall Survival -ORR -Safety
      Exploratory -Changes in quality of life -Healthcare resource utilization throughout the study -Correlation between pretreatment tumor characteristics and response to treatment


      Results:
      Not applicable

      Conclusion:
      Not applicable

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