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C. Matheny



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    MA 10 - Immunotherapy I (ID 664)

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

      11:00 - 12:30  |  Author(s): C. Matheny

      • 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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    OA 17 - Immunotherapy II (ID 683)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      OA 17.07 - Long-Term Survival in Atezolizumab-Treated Patients with 2L+ NSCLC from Ph III Randomized OAK Study (ID 8663)

      14:30 - 16:15  |  Author(s): C. Matheny

      • Abstract
      • Presentation
      • Slides

      Background:
      Atezolizumab (anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. OAK, a Phase III study of atezolizumab vs docetaxel demonstrated superior OS of atezolizumab. The characteristics of the long-term survivors (LTS) in the OAK primary population (n = 850) are evaluated and describe the largest cohort of cancer immunotherapy-treated NSCLC LTS yet reported.

      Method:
      Patients received IV q3w atezolizumab (1200 mg) until PD / loss of clinical benefit or docetaxel (75 mg/m[2]) until PD / unacceptable toxicity. No crossover was allowed. LTS were defined as patients with OS ≥ 24 months and non-LTS as those who died within 24 months of randomization. Patients with OS censored prior to 24 months were not included. Data cutoff, January 23, 2017.

      Result:
      A higher 2-year survival rate was observed for the atezolizumab-arm (31%) vs docetaxel-arm (21%). After a minimum follow-up of 26 months, there were 119 LTS vs 279 non-LTS in the atezolizumab-arm and 77 LTS vs 299 non-LTS in the docetaxel-arm. Characteristics of atezolizumab-arm LTS and non-LTS are shown (Table). Atezolizumab-arm LTS were enriched for non-squamous histology and high PD-L1–expressing tumors, but also included low/no PD-L1–expressing tumors (40.3%). Atezolizumab-arm LTS had higher ORR (39.5%) than non-LTS (5.0%) but included LTS subjects with PD. 52.9% atezolizumab-arm vs 71.4% docetaxel-arm LTS received anti-cancer non-protocol therapy (NPT) after discontinuation of protocol-defined therapy. 51.9% of docetaxel-arm LTS vs 12.7% non-LTS received non-protocol immunotherapy. Median treatment exposure in atezolizumab-arm LTS was 18.0 months. Atezolizumab-arm LTS had a comparable safety profile to all atezolizumab-treated population.

      Conclusion:
      Atezolizumab provides superior 2-year OS benefit vs docetaxel and is well tolerated. The majority of docetaxel-arm LTS received a checkpoint inhibitor as NPT. Atezolizumab LTS appeared to have favorable prognostic factors, including non-squamous histology, but notably were not limited to patients with RECIST v1.1 response or with PD-L1 expression.

      Table. Characteristics of Atezolizumab-Arm Long-Term Survivors (LTS) vs Non-Long Term Survivors (Non-LTS)
      Atezolizumab LTS (n = 119) n (%) Atezolizumab Non-LTS (n = 279) n (%)
      Sex
      Male 61 (51.3) 183 (65.6)
      Female 58 (48.7) 96 (34.4)
      Tobacco use history
      Never smoker 29 (24.4) 47 (16.8)
      Current/previous smoker 90 (75.6) 232 (83.2)
      Histology
      Non-squamous 101 (84.9) 195 (69.9)
      Squamous 18 (15.1) 84 (30.1)
      No. of prior therapies, 1 89 (74.8) 209 (74.9)
      ECOG performance status at baseline
      0 60 (50.4) 89 (31.9)
      1 59 (49.6) 190 (68.1)
      EGFR mutation status, positive 11 (9.2) 26 (9.3)
      PD-L1 IHC subgroup
      TC3 or IC3 28 (23.5) 39 (14.0)
      TC1/2/3 or IC1/2/3 71 (59.7) 156 (55.9)
      TC0 and IC0 48 (40.3) 119 (42.7)
      Best overall response
      Complete response 5 (4.2) 0 (0)
      Partial response 42 (35.3) 14 (5.0)
      Stable disease 47 (39.5) 97 (34.8)
      Progressive disease 25 (21.0) 142 (50.9)
      IC, tumor-infiltrating immune cell; TC, tumor cell. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% 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. NCT02008227.


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