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C. Lewanski



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    MA 10 - Immunotherapy I (ID 664)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 2
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      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): C. Lewanski

      • 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.


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      MA 10.03 - 3-Year Survival and Duration of Response in Randomized Phase II Study of Atezolizumab vs Docetaxel in 2L/3L NSCLC (POPLAR) (ID 8703)

      11:10 - 11:15  |  Author(s): C. Lewanski

      • Abstract
      • Presentation
      • Slides

      Background:
      Atezolizumab (anti–PD-L1) has demonstrated OS benefit over docetaxel in a randomized Phase II study, POPLAR, in patients with advanced NSCLC. This benefit has been confirmed in the randomized Phase III study OAK (Rittmeyer, 2017). The 3-year survival analysis of the POPLAR study presented here describes the longest survival follow-up reported to date of an all-comer randomized PD-L1/PD-1 immunotherapy trial in 2L+ NSCLC.

      Method:
      Patients were randomized 1:1 to receive atezolizumab (1200 mg) or docetaxel (75 mg/m[2]) IV q3w. Tumors were prospectively evaluated for tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression using the VENTANA SP142 IHC assay. Landmark OS was estimated using the Kaplan-Meier method. Data cutoff, April 7, 2017; minimum follow-up, 3 years.

      Result:
      The 2-year and 3-year survival with atezolizumab vs docetaxel were 32.2% vs 16.6% and 18.7% vs 10.0%, respectively. The long-term OS benefit of atezolizumab vs docetaxel was observed across histology and PD-L1 expression subgroups (Table). While the TC3 or IC3 subgroup derived the greatest OS benefit, the TC0 and IC0 subgroup also had improved long-term OS with atezolizumab vs docetaxel. The ITT ORR was 15% in both atezolizumab and docetaxel arms, but the median duration of response was 3 times longer with atezolizumab (22.3 months [95% CI: 11.6, 31.1] vs 7.2 months [95% CI: 5.8, 12.2] with docetaxel). Seven of the 11 docetaxel-arm 3-year survivors received subsequent non-protocol therapy with anti–PD-L1/PD-1 agents. Atezolizumab had a favorable safety profile compared with docetaxel that was consistent with previous reports.

      Conclusion:
      Atezolizumab demonstrates superior 2-year and 3-year OS benefit compared with docetaxel, and this benefit is observed across histology and PD-L1 expression subgroups (including TC0 and IC0). Atezolizumab is well tolerated, and responses are highly durable. These results are consistent with long-term OS results from OAK, presented separately.

      Table. Landmark OS in the ITT, PD-L1 expression, and histology subgroups in POPLAR
      Population (n, atezolizumab vs docetaxel) 2-year OS rate, % 3-year OS rate, %
      Atezolizumab Docetaxel P value[a] Atezolizumab Docetaxel P value[a]
      ITT (144 vs 143) 32.2% 16.6% 0.0027 18.7% 10.0% 0.0419
      PD-L1 Expression Subgroups
      TC3 or IC3 (24 vs 23) 41.7% 19.9% 0.1003 37.5% 14.9% 0.0724
      TC2/3 or IC2/3 (50 vs 55) 36.1% 13.8% 0.0082 21.2% 9.9% 0.1166
      TC1/2/3 or IC1/2/3 (93 vs 102) 36.0% 19.8% 0.0124 18.0% 11.0% 0.1759
      TC0 and IC0 (51 vs 41) 25.0% 6.8% 0.0202 20.5% 6.8% 0.0693
      Histology Subgroups
      Non-squamous (95 vs 95) 32.2% 21.1% 0.0960 23.3% 12.4% 0.0585
      Squamous (49 vs 48) 32.7% 7.8% 0.0020 9.4% 5.2% 0.4603
      [a ]For descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% on TC or IC; TC0 and IC0 = PD-L1 < 1% on TC and IC. NCT01903993.


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