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Manuel Cobo



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    OA05 - Clinical Trials in IO (ID 899)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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      OA05.07 - IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC (ID 12389)

      14:35 - 14:45  |  Author(s): Manuel Cobo

      • Abstract
      • Presentation
      • Slides

      Background

      In addition to the combination of atezolizumab (anti–PD-L1)+platinum+taxane±bevacizumab, non-squamous NSCLC patients may derive benefit from adding atezolizumab to platinum+pemetrexed. The randomized Phase III IMpower132 study (NCT02657434) evaluated first-line pemetrexed+carboplatin or cisplatin±atezolizumab in patients with stage IV non-squamous NSCLC without EGFR or ALK driver mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients were randomized 1:1 to receive 4 or 6 cycles of carboplatin AUC 6 mg/mL/min or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W alone (arm PP) or in combination with atezolizumab 1200 mg Q3W (arm APP), followed by pemetrexed (arm PP) or atezolizumab + pemetrexed (arm APP) maintenance. Atezolizumab could be continued beyond disease progression per protocol guidelines. PFS and OS were co-primary endpoints. Efficacy by PD-L1 expression was an exploratory endpoint. Here, we present investigator-assessed PFS per RECIST v1.1 (final analysis), OS (interim analysis) and safety data.

      4c3880bb027f159e801041b1021e88e8 Result

      292 pts were enrolled in arm APP and 286 pts in arm PP. 43% and 40% in arms APP and PP, respectively, had ECOG PS 0. At the data cutoff (22 May 2018), median follow-up was 14.8 mo overall. PFS analysis showed a statistically significant improvement between arm APP vs PP (median PFS 7.6 vs 5.2 mo; HR=0.596; 95% CI: 0.494, 0.719; P<0.0001). Interim analysis showed a numerical but non-statistically significant OS improvement (Table). Efficacy results were consistent across all key clinical subgroups. Grade 3-4 TRAEs occurred in 53.6% of patients (APP) vs 39.1% (PP). 7.2% of patients (APP) vs 5.1% (PP) had a Grade 5 AE, 3.8% (APP) vs 2.6% (PP) were treatment related. 48.5% of patients (APP) vs 38.0% (PP) experienced AEs of special interest specific to atezolizumab.

      8eea62084ca7e541d918e823422bd82e Conclusion

      IMpower132 met its co-primary endpoint of investigator-assessed PFS in the ITT. Interim OS data (not fully mature) showed numerical improvement. Atezolizumab+pemetrexed+carboplatin or cisplatin was well tolerated, and no new safety signals were identified.

      Table. IMpower132 Efficacy Analyses

      APP Arm
      (atezolizumab+pemetrexed+ carboplatin or cisplatin)
      PP Arm
      (pemetrexed+carboplatin or cisplatin)
      ITT n=292 n=286
      Median PFS (95% CI), mo 7.6 (6.6, 8.5) 5.2 (4.3, 5.6)
      HRa (95% CI; P value) 0.596 (0.494, 0.719; P < 0.0001)
      12-Month PFS (95% CI), % 33.7% (28.2, 39.2) 17.0% (12.6, 21.4)
      Median OS (95% CI), mo 18.1 (13.0, NE) 13.6 (11.4, 15.5)
      HRa (95% CI; P value) 0.813 (0.644, 1.025; P = 0.0797)
      12-Month OS (95% CI), % 59.6% (53.9, 65.3) 55.4% (49.5, 61.2)
      ORR (confirmed, inv-assessed), % 46.9% 32.2%
      DOR (95% CI), mo 10.1 (7.2, 13.3) 7.2 (5.7, 9.0)
      PD-L1–highb n=25 n=20
      Median PFS (95% CI), mo 10.8 (7.9, NE) 6.5 (2.4, 10.6)
      HR (95% CI; P value) 0.464 (0.224, 0.960; P = 0.0339)
      PD-L1–lowb n=63 n=73
      Median PFS (95% CI), mo 6.2 (4.4, 8.4) 5.7 (4.2, 7.9)
      HR (95% CI; P value) 0.804 (0.556, 1.163; P = 0.2462)
      PD-L1–negativeb n=88 n=75
      Median PFS (95% CI), mo 8.5 (6.1, 11.2) 4.9 (4.2, 5.8)
      HR (95% CI; P value) 0.448 (0.313, 0.642; P < 0.0001)

      DOR, duration of response; HR, hazard ratio; inv, investigator; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

      a Stratified. b Baseline tissue available in 60% of patients. PD-L1high (TC3/IC3): patients with PD-L1 expression in ≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells; PD-L1low (TC12/IC12): patients with PD-L1 expression in ≥1% and <50% of tumor cells or ≥1% and <10% of tumor-infiltrating immune cells; and PD-L1negative (TC0/IC0): patients with PD-L1 expression in <1% of tumor cells and <1% of tumor-infiltrating immune cells.

      NCT02657434

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-70 - Efficacy and Safety of Second- or Third-Line Nab-Paclitaxel + Durvalumab in Patients with Advanced NSCLC (ABOUND.2L+) (ID 13042)

      16:45 - 18:00  |  Author(s): Manuel Cobo

      • Abstract

      Background

      Cytotoxic chemotherapy may enhance the effect of immune checkpoint blockers (ICBs) through interaction with the immune system (immunostimulation) and cancer cells (increased antigenicity). The phase II ABOUND.2L+ trial investigated second-/third-line nab-paclitaxel monotherapy, nab-paclitaxel + CC-486, or nab-paclitaxel + durvalumab in patients with previously treated advanced-stage NSCLC. This report presents an updated analysis of the efficacy and safety from the nab-paclitaxel + durvalumab treatment arm.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients ≥ 18 years with advanced NSCLC and no more than 1 prior line of platinum-containing chemotherapy (ICBs in prior line, first/second, allowed) were included. Patients were treated with nab-paclitaxel on days 1 and 8 + durvalumab 1125 mg on day 15 of a 21-day cycle until unacceptable toxicity or progressive disease as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or immune-related RECIST v1.1. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 79 patients were assigned to nab-paclitaxel + durvalumab. The median age of patients in that arm was 63.0 years; 68.4% were male, 97.5% were white, 77.2% had ECOG performance status 1, and 69.6% had nonsquamous histology; 8 patients received prior ICBs. Median and 1-year PFS were 4.5 months (95% CI: 3.45-5.88) and 25.7% (95% CI 16.3-36.2); median PFS in those with and without prior ICB treatment was NE (95% CI 1.38-NE) and 4.4 months (95% CI 2.96-5.68) and in those with squamous and nonsquamous histology was 6.0 months (95% CI 2.99-7.75) and 4.2 months (95% CI 2.86-5.75). The ORR was 27.8%, and DCR was 70.9%. Median OS was 10.1 months (95% CI: 7.75-NE). Median percentage of per protocol dose was 87.5% for nab-paclitaxel and 82.9% for durvalumab. All patients had at least 1 treatment-emergent adverse event (TEAE), and 67.9% had at least 1 grade 3 or 4 TEAE. Common TEAEs of special interest (all grades) included peripheral neuropathy (grouped term; 37.2%), diarrhea (34.6%), anemia (30.8%), dyspnea (25.6%), nausea (24.4%), cough (24.4%), pyrexia (19.2%), and neutropenia (17.9%). TEAEs leading to dose interruption/reduction (nab-paclitaxel and/or durvalumab) were reported in 73.1% of patients, and those leading to discontinuation in 11.5%.

      8eea62084ca7e541d918e823422bd82e Conclusion

      nab-Paclitaxel + durvalumab demonstrated promising antitumor activity and manageable toxicity in second- or third-line treatment of patients with advanced NSCLC. NCT02250326.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.01-93 - Quality of Life in Patients with Advanced NSCLC Treated in Second- or Third-Line with Nab-Paclitaxel + Durvalumab: ABOUND.2L+ (ID 12993)

      16:45 - 18:00  |  Author(s): Manuel Cobo

      • Abstract

      Background

      Quality of life (QoL) can be adversely affected in patients with advanced NSCLC, particularly those receiving second- or third-line treatment. In these patients, checkpoint inhibitors are a recommended treatment option. Through multiple mechanisms, including the release of tumor antigens via tumor cell lysis, chemotherapy can augment immunotherapeutic effects, which is the rationale for combining chemotherapy with immunotherapy agents. The phase II ABOUND.2L+ trial investigated second- or third-line nab-paclitaxel either alone or in combination with CC-486 or durvalumab in patients with advanced NSCLC. The objective of this analysis is to report QoL outcomes in patients treated with nab-paclitaxel + durvalumab from the ABOUND.2L+ trial.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Enrolled patients were ≥ 18 years with advanced NSCLC and no more than 1 prior line of platinum-containing chemotherapy. Immunotherapy in a prior line, first or second, was allowed. Patients were treated with nab-paclitaxel on days 1 and 8 + durvalumab 1125 mg on day 15 of a 21-day cycle. Treatment continued until unacceptable toxicity or disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or immune-related RECIST v1.1. The primary endpoint was progression-free survival. QoL was a prespecified exploratory endpoint assessed using the Lung Cancer Symptom Scale (LCSS), EuroQol 5D-5L, and EORTC QLQ-C30 on day 1 of each cycle, and was examined through 6 cycles of treatment for this analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 79 patients were assigned to the nab-paclitaxel + durvalumab arm. The median age was 63.0 years. Most patients were white (97.5%), male (68.4%), and had ECOG PS of 1 (77.2%). For the entire study, baseline and ≥ 1 postbaseline QoL assessments were completed by 58 (73.4%) patients. 41 patients completed 6 cycles of treatment with nab-paclitaxel + durvalumab. After cycle 6, the mean change from baseline in LCSS total score and pulmonary symptom score was 0.1 and −0.2, respectively. LCSS hemoptysis score improved relative to baseline at every treatment cycle; mean change from baseline after 6 cycles was 0.8. Mean change from baseline in the EuroQol 5D-5L visual analog scale score and EORTC QLQ-C30 global health status/QoL scale score after 6 cycles of treatment was 2.5 and −1.19, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In general, patients with advanced NSCLC treated with second- or third-line nab-paclitaxel + durvalumab maintained their QoL through 6 cycles of treatment. NCT02250326.

      6f8b794f3246b0c1e1780bb4d4d5dc53