Virtual Library

Start Your Search

T.J. Ong



Author of

  • +

    MA 03 - Chemotherapy (ID 651)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      MA 03.01 - Nab-Paclitaxel ± CC-486 as Second-Line Treatment of Advanced NSCLC: Results from the ABOUND.2L+ Study (ID 8676)

      11:00 - 11:05  |  Author(s): T.J. Ong

      • Abstract
      • Presentation
      • Slides

      Background:
      CC-486 (oral azacitidine) is an epigenetic modifier with potential effect as a priming agent for chemotherapy in patients with NSCLC. Outcomes of nab-paclitaxel+CC-486 vs nab-paclitaxel as second-line treatment of advanced NSCLC are reported.

      Method:
      Patients with advanced nonsquamous NSCLC and no more than 1 prior chemotherapy line (including platinum doublet combination) were randomized (1:1) to nab-paclitaxel 100 mg/m[2] d8, 15 + CC-486 200 mg qd d1-14 or nab-paclitaxel 100 mg/m[2] d1, 8, both administered q3w until progressive disease/unacceptable toxicity. Primary endpoint was PFS. Secondary endpoints: DCR, ORR, OS, and safety. QoL, an exploratory endpoint, was assessed on d1 of each cycle.

      Result:
      The nab-paclitaxel+CC-486 arm was discontinued in October 2016 due to demonstrated futility vs nab-paclitaxel monotherapy upon completion of a protocol-specified interim analysis. Overall, 161 patients were randomized (nab-paclitaxel+CC-486, 81; nab-paclitaxel, 80). Baseline characteristics were balanced between arms. The median number of cycles was 4 for each arm, and the median nab-paclitaxel cumulative dose was 600 mg/m[2] and 800 mg/m[2] in the nab-paclitaxel+CC-486 and nab-paclitaxel arms, respectively. Rates of grade 3/4 (G3/4) treatment-emergent AEs were 59.5% and 54.4% for the combination and monotherapy arms, respectively. The most frequent hematologic G3/4 AEs were neutropenia (16.5% vs 10.1%) and anemia (1.3% vs 7.6%). G3/4 peripheral neuropathy was reported in 2.5% and 7.6% of patients, respectively. The addition of CC-486 to nab-paclitaxel did not improve ORR, DCR, PFS, or OS (Table). When assessed by Lung Cancer Symptom Scale, nab-paclitaxel monotherapy was associated with improvement in the global QoL, average symptom burden index, and lung cancer symptoms except for hemoptysis.

      Conclusion:
      The addition of CC-486 to nab-paclitaxel did not clinically benefit patients with previously treated NSCLC. However, single-agent nab-paclitaxel appears to be a promising therapy based on safety, efficacy, and QoL data. Updated efficacy and safety data will be presented. NCT02250326

      nab-Paclitaxel + CC-486 n = 81 nab-Paclitaxel n = 80
      Median PFS, months 3.2 4.2
      HR (95% CI) 1.3 (0.9 - 2.0)
      1-year PFS, % 4.1 18.3
      Median OS, months 8.4 12.7
      HR (95% CI) 1.4 (0.88 - 2.31)
      1-year OS, % 39.2 54.3
      ORR, n (%)[a] 11 (13.6) 11 (13.8)
      Response rate ratio (95% CI) 0.99 (0.45 - 2.15)
      CR PR SD PD DCR (≥ SD) 0 11 (13.6) 41 (50.6) 22 (27.2) 52 (64.2) 0 11 (13.8) 43 (53.8) 19 (23.8) 54 (67.5)
      CR, complete response; DCR, disease control rate; HR, hazard ratio; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. [a] Response rate was based on the intent-to-treat population; however, 14 patients did not have a response assessment.


      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    MA 10 - Immunotherapy I (ID 664)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
    • +

      MA 10.02 - Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+ (ID 8682)

      11:05 - 11:10  |  Author(s): T.J. Ong

      • Abstract
      • Presentation
      • Slides

      Background:
      Chemotherapy may enhance immunotherapeutic effects by causing tumor antigen release, which primes the immune system to kill tumor cells. Early clinical data on nab-paclitaxel + carboplatin in combination with immune checkpoint inhibitors (ICI) demonstrated promising activity without compounding toxicities in patients with non-small cell lung cancer (NSCLC). ABOUND.2L+ evaluated nab-paclitaxel–based regimens in previously treated patients with advanced NSCLC. Here we report the efficacy and safety of nab-paclitaxel + durvalumab as second/third-line treatment.

      Method:
      Patients with advanced NSCLC were assigned to receive second/third-line (immunotherapy allowed in prior line, including platinum doublet combination) nab-paclitaxel 100 mg/m[2] on days 1 and 8 + durvalumab 1125 mg on day 15, in 21-day cycles, administered until unacceptable toxicity/progression per immune-related RECIST v1.1. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety.

      Result:
      Seventy-nine patients were enrolled. Median age was 63 years, 68% of patients were male, 23% had Eastern Cooperative Oncology Group performance status of 0, and 70% had nonsquamous NSCLC; 11% of patients received prior ICIs. Median PFS (Table) and OS were 4.5 (3.4-5.8) months and NE (7.3-NE). ORR was 27% (1 complete response) and DCR was 71%. Grade 3/4 treatment-emergent adverse events of special interest occurring in ≥ 5% of patients included neutropenia (6%) and dyspnea (5%); grade 3/4 peripheral neuropathy and anemia each occurred in 4% of patients. Median treatment duration was 24 weeks; median number of treatment cycles was 7. For nab-paclitaxel and durvalumab, median dose intensities were 59.05 mg/m[2]/week and 326.61 mg/week, respectively; median percentages of per-protocol dose were 88.58% and 87.10%.

      Conclusion:
      The combination of durvalumab with nab-paclitaxel demonstrated antitumor activity with manageable toxicity in the second/third-line setting. Further details will be presented. NCT02250326

      Nab-P Durva Median PFS (range), months
      Overall (n = 79) 4.5 (3.4-5.8)
      ICI pretreated (n = 9)[a] ICI naive (n = 69)[a] 6.9 (1.4-NE) 4.4 (3.0-5.7)
      Squamous (n = 23)[a] Nonsquamous (n = 55)[a] 5.9 (3.0-7.8) 4.2 (2.9-5.7)
      ICI, immune checkpoint inhibitor; NE, not estimable; PFS, progression-free survival. [a] Data pending for 1 patient.


      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 4
    • +

      P2.01-004 - Safety and Efficacy of Nab-Paclitaxel plus Carboplatin in Elderly Patients with NSCLC (ABOUND.70+) (ID 7561)

      09:00 - 09:00  |  Author(s): T.J. Ong

      • Abstract
      • Slides

      Background:
      A subanalysis of a phase III registrational trial demonstrated a 9.5-month survival benefit with nab-paclitaxel/carboplatin vs paclitaxel/carboplatin for patients ≥70 years with advanced NSCLC. ABOUND.70+ evaluated 2 schedules of nab-paclitaxel/carboplatin to determine whether a 1-week break could improve tolerability.

      Method:
      Patients ≥70 years with locally advanced/metastatic NSCLC were randomized to receive first-line nab-paclitaxel 100mg/m[2] on days 1, 8, 15 and carboplatin AUC 6 on day 1 of a 21-d cycle (Arm A) or the same regimen with a 1-week break between cycles (Arm B). Primary endpoint: the percentage of patients with grade ≥2 peripheral neuropathy or grade ≥3 myelosuppression; key secondary endpoints: progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), for which statistical analyses did not control for type I error (P values unadjusted).

      Result:
      At interim evaluation, the primary endpoint was similar across treatment arms leading to early closure of enrollment. Baseline characteristics were well balanced between arms (Arm A, n = 71; Arm B, n = 72). Primary endpoint results are presented in the table. Overall, confirmed ORR was 23.9% vs 40.3% (P = 0.038), median PFS was 3.6 vs 7.0 months (HR 0.48 [95% CI, 0.30-0.76]; P = 0.002), and median OS was 15.2 vs 16.2 months (HR 0.72 [95% CI, 0.44-1.19]; P = 0.197). Among patients who received second-line therapy across treatment arms (n = 61), median OS from start of first-line treatment was 22.7 months (95% CI, 11.79-not estimable [NE]) and 16.4 months (95% CI, 12.12-NE) in patients receiving chemotherapy and immunotherapy, respectively.

      Conclusion:
      nab-Paclitaxel/carboplatin was well tolerated and efficacious in elderly patients with advanced NSCLC. Incidence of grade ≥2 peripheral neuropathy or grade ≥3 myelosuppression (primary endpoint) was similar in both treatment arms. A signal of improvement was observed in PFS and ORR in Arm B. NCT02151149

      Primary Endpoint
      Event, n (%) Arm A n = 68 Arm B n = 70
      Patients with either grade ≥ 2 peripheral neuropathy or grade ≥ 3 myelosuppression 52 (76.5) 54 (77.1)
      Grade ≥ 2 peripheral neuropathy 25 (36.8) 25 (35.7)
      Grade ≥ 3 myelosuppression 48 (70.6) 45 (64.3)
      Neutropenia 39 (57.4) 39 (55.7)
      Anemia 14 (20.6) 17 (24.3)
      Thrombocytopenia 17 (25.0) 12 (17.1)


      Only Active 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 or select "Add to Cart" and proceed to checkout.

    • +

      P2.01-013 - Nab-Paclitaxel/Carboplatin in Elderly Patients with NSCLC (ABOUND.70+): Analysis of Safety and Quality of Life (QoL) by Cycle (ID 8185)

      09:00 - 09:00  |  Author(s): T.J. Ong

      • Abstract

      Background:
      ABOUND.70+ evaluated 2 schedules of first-line nab-paclitaxel/carboplatin in patients ≥70 years with advanced NSCLC to determine whether a 1-week break can improve tolerability. Safety and QoL by cycle are reported.

      Method:
      Patients ≥70 years with locally advanced/metastatic NSCLC were randomized to first-line nab-paclitaxel 100mg/m[2] on d1, 8, 15 and carboplatin AUC 6 on d1 of a 21-d cycle (Arm A) or the same regimen with a 1-week break between cycles (Arm B). Primary endpoint: percentage of patients with grade ≥2 peripheral neuropathy (PN) or grade ≥3 myelosuppression (laboratory values). QoL (exploratory endpoint) was assessed using Lung Cancer Symptom Scale (LCSS) on d1 of each cycle. Safety analyses included patients receiving ≥1 dose of study medication. AEs/QoL were analyzed at each of the first 6 cycles.

      Result:
      At interim evaluation, primary endpoint was similar across arms, resulting in early closure of enrollment. Of 143 randomized patients, 68 and 70 in Arms A and B received ≥1 dose of study drug. Table lists primary endpoint and key safety results by cycle. Grade ≥2 PN occurred earlier in Arm A. Incidence of grade ≥3 myelosuppression was highest in the first 2 cycles, progressively declining after cycle 3 (both arms). Dose reductions occurred in earlier cycles for Arm A; at the start of cycle 4, 36% vs 47% of patients received the maximum dose (100mg/m[2]) of nab-paclitaxel in Arms A and B. Generally, QoL was maintained throughout treatment. LCSS item of cough improved with each cycle; mean change from baseline at the end of cycle 6 was 25.4 and 13.8mm (visual analog scale).

      Conclusion:
      Although the overall rate of grade ≥2 PN and grade ≥3 myelosuppression was similar between arms, analysis by cycle showed that grade ≥2 PN and dose reductions occurred earlier in Arm A. QoL was maintained in both arms. NCT02151149

      Arm A n = 68 Arm B n = 70
      Safety
      Primary endpoint, % 76 77
      P value 0.9258
      Peripheral neuropathy, % Grade ≥ 2[a] Grade ≥ 3[a] Grade ≥ 2[a] Grade ≥ 3[a]
      All cycles 37 13 36 17
      Cycle 1 6 0 0 0
      Cycle 2 6 4 1 0
      Cycle 3 7 4 9 1
      Cycle 4 4 0 7 1
      Cycle 5 6 3 4 1
      Cycle 6 4 1 4 9
      Myelosuppression, % Grade ≥ 3 Grade ≥ 3
      All cycles 71 64
      Cycle 1 35 37
      Cycle 2 22 10
      Cycle 3 3 10
      Cycle 4 6 1
      Cycle 5 1 3
      Cycle 6 3 3
      [a ]Calculated by first occurrence of adverse event of respective grade.
      .

    • +

      P2.01-014 - ABOUND.PS2: Safety and Efficacy of Nab-Paclitaxel–Based Therapy in Patients with NSCLC and ECOG PS 2 (ID 8186)

      09:00 - 09:00  |  Author(s): T.J. Ong

      • Abstract

      Background:
      Patients with advanced NSCLC with poor ECOG PS can benefit from platinum-based doublet chemotherapy, although limited data exist from recent, randomized prospective trials. ABOUND.PS2 evaluated the safety and efficacy of nab-paclitaxel/carboplatin induction followed by nab-paclitaxel monotherapy in patients with advanced NSCLC and ECOG PS 2.

      Method:
      Chemotherapy-naive patients with histologically/cytologically confirmed stage IIIB/IV NSCLC and ECOG PS 2 received 4 cycles of nab-paclitaxel 100 mg/m[2] on days 1 and 8 plus carboplatin AUC 5 on day 1 q3w. Patients not progressing could receive monotherapy with nab-paclitaxel 100 mg/m[2] on days 1 and 8 q3w until progression or unacceptable toxicity. Primary endpoint: percentage of patients discontinuing within the first 4 cycles due to treatment-emergent adverse events (TEAEs). Other endpoints: progression-free survival (PFS), disease control rate (DCR), overall survival (OS), overall response rate (ORR), and quality of life (QoL) by Lung Cancer Symptom Score (LCSS).

      Result:
      Forty patients were treated. Median age was 67.5 years, 60.0% were male, 92.5% were white, and 62.5% had nonsquamous histology. During induction, 11 of 40 patients (28%) discontinued due to TEAEs (primary endpoint). In total, 16 of 40 patients (40.0%) received nab-paclitaxel as monotherapy. In all treated patients, the median percentage of per-protocol dose of nab-paclitaxel was 78.3% and the median nab-paclitaxel dose intensity was 52.2 mg/m[2]/week (planned, 66.7 mg/m[2]/week). See table for additional safety, efficacy, and QoL results.

      Conclusion:
      These results support the role of this nab-paclitaxel–based regimen in patients with NSCLC and ECOG PS 2. The regimen was well tolerated and appears to have resulted in a clinically meaningful improvement in QoL. Compared with historical data, this regimen is active in patients with stage IIIB/IV NSCLC and ECOG PS 2. NCT02289456

      All Treated Patients N = 40
      Safety
      Grade ≥ 3 TEAEs of special interest, n (%) Neutropenia Anemia Thrombocytopenia Peripheral neuropathy 9 (22.5) 7 (17.5) 2 (5.0) 1 (2.5)
      Efficacy
      PFS, median (95% CI), months 4.4 (2.99-7.00)
      OS, median (95% CI), months 7.66 (4.93-13.17)
      ORR (RECIST v1.1), n (%) 12 (30.0)
      DCR, % Complete response Partial response Stable disease Progressive disease, % Patients with no postbaseline tumor assessment 30 (75.0) 0 12 (30.0) 18 (45.0) 2 (5.0) 8 (20.0)
      QoL
      Mean maximum improvement from baseline
      LCSS Global QoL item, mm[a] 16.91
      [a] A ≥ 10-mm improvement was considered clinically meaningful.

    • +

      P2.01-015 - Longitudinal Assessment of Performance Status (PS) in Patients with NSCLC and ECOG PS 2 on Nab-Paclitaxel–Based Therapy (ID 8187)

      09:00 - 09:00  |  Author(s): T.J. Ong

      • Abstract

      Background:
      ABOUND.PS2 evaluated nab-paclitaxel/carboplatin induction followed by nab-paclitaxel monotherapy in patients with advanced NSCLC and ECOG PS 2. Concordance between patient- and physician-reported PS as well as change in PS with chemotherapy were assessed longitudinally.

      Method:
      Chemotherapy-naive patients with histologically/cytologically confirmed stage IIIB/IV NSCLC and ECOG PS 2 received 4 cycles of nab-paclitaxel 100 mg/m[2] on days 1 and 8 plus carboplatin AUC 5 on day 1 q3w. Patients not progressing could receive monotherapy with nab-paclitaxel 100 mg/m[2] on days 1 and 8 q3w until progression or unacceptable toxicity. Primary endpoint was the percentage of patients discontinuing within the first 4 cycles due to treatment-emergent adverse events. ECOG PS was assessed by patients on day 1 of each cycle and at treatment discontinuation, and ECOG PS and spirometry were assessed by physicians at screening, on day 1 of each cycle, and at treatment discontinuation.

      Result:
      Forty patients were treated. Baseline ECOG PS was reported as 2 by 48% and 95% of patients and physicians, respectively. Only 53% of patients rated their ECOG PS the same as the physician at cycle 1 day 1. For patients with both pre- and post-treatment ECOG assessments, 14 of 33 patients (42%) and 12 of 38 physicians (32%) reported an improvement from baseline at least once during treatment (Figure). At baseline, physicians believed that ECOG PS would be reversible with treatment in the majority of patients (80%). Mean FEV1 was 1.29 L and mean PEF was 2.66 L/s at baseline; exploratory investigations of spirometry data indicate that lung function (FEV1 and PEF) remained stable over the course of treatment.

      Conclusion:
      These results from the ABOUND.PS2 study suggest that patient-reported PS assessments may differ from physician assessments. Improvements in ECOG PS were reported by both patients and physicians during treatment. NCT02289456Figure 1