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Melanie Wain Kier

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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.11 - STK11/LKB1 Genomic Alterations Are Associated with Inferior Clinical Outcomes with Chemo-Immunotherapy in Non-Squamous NSCLC (Now Available) (ID 2898)

      14:00 - 15:30  |  Author(s): Melanie Wain Kier

      • Abstract
      • Presentation
      • Slides


      Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread use of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we present updated data on the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy from a large retrospective multi-institution international study.


      620 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 21 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 468 pts treated with first-line CPP (or >1st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 152 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP.


      Among 468 CPP-treated pts, STK11/LKB1 genomic alterations (N=118) were associated with significantly shorter PFS (mPFS 5.0m vs 6.8m, HR 1.45, 95% CI 1.11 to 1.91; P=0.007) and shorter OS (mOS 10.6m vs 16.7m, HR 1.46, 95% CI 1.04 to 2.07; P=0.031) compared with STK11/LKB1-wt tumors (N=350). The likelihood of disease progression as BOR to CPP differed significantly between the two groups (29.5% vs 17%, P= 0.006). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N=435) (mPFS 5.0m vs 6.9m, HR 1.48, 95% CI 1.12-1.95, P=0.006 and mOS 10.6m vs 16.7m, HR 1.45, 95% CI 1.02-2.05, P=0.036). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not result in significant improvement of PFS (mPFS 5.0m vs 3.9m, HR 0.82, 95% CI 0.63 to 1.07, P=0.14) or OS (mOS 10.6m vs 9.1m, HR 0.93, 95% CI 0.67 to 1.30, P=0.69) compared to CP alone.


      In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-63 - Impact of Prior Radiation Pneumonitis on Incidence of Immunotherapy Related Pneumonitis (ID 662)

      09:45 - 18:00  |  Author(s): Melanie Wain Kier

      • Abstract


      Patients with a history of radiation pneumonitis (RP) requiring steroids have generally been excluded from immuno-oncology (IO) trials of PD-1/PDL-1 monoclonal antibodies for safety concerns. The risk of IO-associated pneumonitis (IOP) in this group of patients (pts) is therefore unknown. We evaluated the frequency of IOP in pts who had prior RP.


      We evaluated all pts with non-small cell lung carcinoma (NSCLC) treated at our institution between 2011 and 2018 who were diagnosed with RP and at a later point received IO. Demographics, tumor characteristics, steroid use and outcomes were extracted from the electronic medical record. Median overall survival (mOS), median progression free survival (mPFS), and median time to treatment failure (mTTF) from the start of IO were estimated from Kaplan-Meier curves.


      We identified 29 pts: median age at diagnosis 63 yrs, 51.7% male, none had received prior targeted therapies. IO treatments were: atezolizumab (2), durvalumab (2), nivolumab (12), and pembrolizumab (13). Median time from RP diagnosis to start of IO was 14.2mo (2.2-75 mo). 23 pts (79%) had experienced prior grade ≥ 2 RP requiring steroids. Only 2 of the 29 pts (6.9%) developed IOP. Both pts had required steroids for prior RP and both received durvalumab; one pt was on prednisone ≥ 10mg at the start of IO. Both required steroid treatment of IOP, are still on IO and have not progressed (censored at 8.3mo and 9.9mo). OS and PFS after IO are similar (Table 1) whether or not pts required treatment for RP or were on prednisone ≥ 10 mg (or steroid equivalent) at the start of IO.

      Table 1: IO outcomes based on RP history and steroid use at start of IO

      RP Grade ≥ 2

      n=23 (95% CI)

      RP Grade < 2

      n=6 (95% CI)

      Prednisone ≥ 10mg

      n=7 (95% CI)

      Prednisone < 10mg

      n=22 (95% CI)

      All patients

      n = 29 (95% CI)

      mPFS (mo)

      5.44 (2.1-12.6)

      12.95 (0.95-)

      6.16 (2-)

      5.44 (2.1-)

      6.16 (2.4-)

      mOS (mo)

      6.6 (3.93-13.8)


      14.3 (5.3-)

      8 (3.4-16.8)

      8 (5.3-15)

      mTTFa (mo)

      2.3 (1.9-4.8)

      2.3 (1.9-)

      4.4 (2-)

      2.3 (1.9-10.9)

      2.75a (2-7)

      an=28: 1 pt lost to follow up after start of IO


      In our cohort, the incidence of IOP after RP is low and similar to the rate of pneumonitis reported with pembrolizumab in pts with prior exposure to thoracic radiation.