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Alan Sandler



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    OA01 - Improving Outcomes in Locoregional NSCLC I (ID 892)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 107
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      OA01.06 - DETERRED:  Phase II Trial Combining Atezolizumab Concurrently with Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer (ID 12842)

      11:25 - 11:35  |  Author(s): Alan Sandler

      • Abstract
      • Presentation
      • Slides

      Background

      While consolidation immunotherapy after chemoradiation (CRT) is the current standard of care for locally advanced NSCLC (LA-NSCLC), the effectiveness of immunotherapies may be enhanced when combined concurrently with CRT. We report on the safety and preliminary efficacy of combining PD-L1 blockade using atezolizumab (atezo) and concurrent CRT followed by consolidation full dose carboplatin/paclitaxel (CP) with atezo and maintenance atezo up to 1 year for LA-NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a single institution phase II study in LA-NSCLC assessing the safety and feasibility of adding atezo to CRT in two parts: I) sequentially (N=10) with CP after completing CRT, or II) concurrently (N=30) with CRT followed by consolidation atezo with CP. Atezo was given at 1200 mg IV Q3 weeks for up to one year from the first dose. Radiation dose at 60-66 Gy in 30-33 fractions was combined with weekly low dose CP, followed by 2 cycles of full dose CP. Severe adverse events (AEs) ≥ grade 3 are defined within 15 weeks of start of therapy or any immune-related AEs during atezo treatment. Evaluable patients (pts) have received at least one dose of atezo.

      4c3880bb027f159e801041b1021e88e8 Result

      From February 2016 to April 2018, we accrued 40 evaluable pts. For part 1, any grade 3+ AEs was seen in 6 pts (60%), with most common being pneumonia (2 of 10, 20%). Three grade 3+ AEs (30%) were attributed to atezo, including dyspnea, arthralgia and a grade 5 TE fistula. Grade 2 radiation pneumonitis (RP) was seen in 3 pts. Four progressed with disease during atezo maintenance and have died, ranging from 0.93 to 1.86 years. Four pts completed atezo and are in follow up without recurrence. For part 2, 17 of 30 pts had any grade 3+ AEs (57%), with pneumonia being the most common (6 of 30, 20%). Three (10%) were attributed to atezo (dyspnea, fatigue and heart failure). RP was seen in 3 pts, with 2 grade 2 and 1 grade 3, which led to atezo discontinuation. So far, 4 pts have progressed and 4 have died, 2 due to disease and 2 due to treatment (neutropenic sepsis and gastric hemorrhage). All others have completed CRT and are on maintenance atezo, ranging from 5 to 19 doses. Updated efficacy results will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Concurrent atezo with CRT followed by consolidation and maintenance atezo appears safe without increased toxicities compared to CRT alone followed by consolidation and maintenance atezo.

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-33 - Retrospective Descriptive Analysis of Metformin with Atezolizumab in Advanced Non-Small Cell Lung Cancer in The OAK Trial (ID 12388)

      16:45 - 18:00  |  Author(s): Alan Sandler

      • Abstract
      • Slides

      Background

      The randomized Phase III OAK trial investigated atezolizumab (anti–PD-L1) for treatment of advanced or metastatic previously-treated NSCLC. Atezolizumab significantly improved OS compared with docetaxel. Given that emerging studies have identified an association between metformin use and antitumor activity/immune interactions, we retrospectively explored metformin use in patients in the OAK study.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients received atezolizumab (1200 mg IV every 3 weeks [q3w]) until PD or loss of clinical benefit or docetaxel (75 mg/m2 IV q3w) until PD/unacceptable toxicity. Patients who received atezolizumab or docetaxel and did or did not receive metformin as concomitant therapy were retrospectively evaluated for ORR, PFS and OS (data cutoff, July 7, 2016). Unadjusted and adjusted comparisons between metformin users and non-metformin users were done.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 425 patients randomized to atezolizumab, 36 received metformin; of the 425 patients randomized to docetaxel, 35 received metformin. Key baseline characteristics are shown in the table. Most metformin users started metformin before or within 30 days of study start (92% and 7% respectively). There was a numerical improvement in ORR in Atezo-Met patients compared with Atezo-NoMet patients (25% vs 13%; unadjusted P = 0.038 [adjusted = 0.093]), whereas there was no statistically significant improvement in ORR in Doc-Met patients compared with Doc-NoMet patients (17% vs 13%; unadjusted P = 0.499 [adjusted = 0.295]). There were no observable differences in PFS or OS in either the Atezo-Met vs Atezo-NoMet or Doc-Met vs Doc-NoMet groups (median PFS, 2.8 vs 2.8 mo and 4.2 vs 4.0 mo, respectively; median OS, 12.6 vs 14.1 mo and 9.1 vs 9.7 mo, respectively).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Encouraging response rates suggest patients may benefit from receiving concomitant metformin treatment with atezolizumab. Lack of difference in PFS and OS may be due to lack of treatment effect or lack of statistical power and requires further prospective investigation.

      Table. Characteristics of Patients Who Received Atezolizumab (Atezo) or Docetaxel (Doc) Combined With Metformin (Met) or No-Metformin (NoMet)

      Atezo-Met, n (%) (n = 36)

      Atezo-NoMet, n (%) (n = 389)

      Doc-Met, n (%)
      (n = 35)

      Doc-NoMet, n (%)
      (n = 390)

      Diabetes mellitus type 2

      33 (91.6)

      28 (7.2)

      33 (94.3)

      26 (6.7)

      Sex

      Male

      28 (77.8)

      233 (59.9)

      28 (80.0)

      231 (59.2)

      Female

      8 (22.2)

      156 (40.1)

      7 (20.0)

      159 (40.8)

      Tobacco use history

      Never smoker

      2 (5.6)

      82 (21.1)

      2 (5.7)

      70 (17.9)

      Current/previous smoker

      34 (94.4)

      307 (78.9)

      33 (94.3)

      320 (82.1)

      Histology

      Nonsquamous

      22 (61.1)

      291 (74.8)

      21 (60.0)

      294 (75.4)

      Squamous

      14 (38.9)

      98 (25.2)

      14 (40.0)

      96 (24.6)

      No. of prior therapies

      1

      30 (83.3)

      290 (74.6)

      24 (68.6)

      296 (75.9)

      ECOG performance status at baseline

      0

      15 (41.7)

      140 (36.0)

      12 (34.3)

      148 (37.9)

      1

      21 (58.3)

      249 (64.0)

      23 (65.7)

      242 (62.1)

      EGFR mutation status

      Positive

      1 (2.8)

      41 (10.5)

      1 (2.9)

      42 (10.8)

      PD-L1 IHC subgroup

      TC3 or IC3
      (PD-L1 ≥ 50% TC or 10% IC)

      11 (30.6)

      61 (15.7)

      5 (14.3)

      60 (15.4)

      TC1/2/3 or IC1/2/3
      (PD-L1 ≥ 1% on TC or IC)

      27 (75.0)

      214 (55.0)

      19 (54.3)

      203 (52.1)

      TC0 and IC0
      (PD-L1 < 1% on TC and IC)

      9 (25.0)

      171 (44.0)

      16 (45.7)

      183 (46.9)

      TC, tumor cell; IC, tumor-infiltrating immune cell.
      6f8b794f3246b0c1e1780bb4d4d5dc53

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