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Robert McEwen



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    OA07 - Precision Medicine Involves Biology and Patients (ID 132)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      OA07.02 - LKB1 Mutations in Metastatic Non-Small Cell Lung Cancer (mNSCLC): Prognostic Value in the Real World (Now Available) (ID 902)

      11:00 - 12:30  |  Author(s): Robert McEwen

      • Abstract
      • Presentation
      • Slides

      Background

      Despite recent advances in treating mNSCLC, many patients fail to respond. Identifying genetic markers may help maximize clinical benefit and avoid unnecessary toxicity. LKB1/STK11 alterations (LKB1m) and co-occurring KRAS mutations/LKB1 loss (KRAS/LKB1) have been associated with poor outcomes in patients treated with immunotherapy (IO). Among chemotherapy-treated patients, however, the prognostic value is less understood. This retrospective study examined LKB1m, KRAS/LKB1 and outcomes in patients with mNSCLC receiving IO (as monotherapy or in combination) or chemotherapy in the real-world setting.

      Method

      Adult patients with mNSCLC who initiated first line (1L) treatment between Jan 2013 and Jun 2017 and had been profiled with the FoundationOne assay in routine care were enrolled from the Flatiron Health Oncology electronic medical record database. Associations between LKB1m, LKB1/KRAS and overall survival (OS) or progression-free survival (PFS) were evaluated by line of therapy (1L and second line [2L]) according to histology (non-squamous/squamous and non-squamous only) using multivariate Cox proportional hazards models. All analyses were stratified by IO or chemotherapy.

      Result

      2407 patients (1847 non-squamous) were included; average age was 66.1 years at 1L initiation. 328 (13.6%) patients harbored LKB1m and 157 (6.5%) harbored KRAS/LKB1. Among IO-treated patients in the 2L setting, LKB1m was associated with shorter OS and PFS versus wild type. A similar association was observed in the 1L setting and in the non-squamous only subgroup. In patients receiving chemotherapy, LKB1m was associated with worse outcomes only in the 1L setting. All associations were generally more pronounced among KRAS/LKB1 compared with LKB1m patients.

      Table. Association between LKB1m and OS or PFS in mNSCLC stratified by IO or chemotherapy and lines of therapy
      Mutation group
      LKB1m
      All mNSCLC Non-Squamous
      Outcome IO Chemotherapy IO Chemotherapy
      1L (n = 270) 2L (n = 670) 1L (n =2,137) 2L (n = 863) 1L (n = 187) 2L (n = 498) 1L (n = 1,687) 2L (n = 683)
      LKB1m, N (%) 40 (14.8) 111 (16.6) 288 (13.5) 83 (9.6) 38 (20.3) 97 (19.5) 257 (15.2) 75 (11.0)
      OS
      Median 341 192 340 350 431 201 356 400
      (IQR) (221 – NA) (72 – 523) (284 – 405) (307 – 451) (221 – NA) (73 – 613) (287 – 415) (307 – 453)
      HR 1.43 1.59 1.40 1.07 1.40 1.67 1.43 1.05
      (95% CI) (0.90 – 2.27) (1.25 – 2.03) (1.21 – 1.63) (0.81 – 1.41) (0.84 – 2.32) (1.27 – 2.19) (1.22 – 1.68) (0.78 – 1.42)
      PFS
      Median 122 67 136 122 125 68 136 128
      (IQR) (83 – 295) (46 – 118) (119 – 146) (97 – 147) (81 – 299) (46 – 114) (122 – 149) (98 – 153)
      HR 1.43 1.59 1.40 1.07 1.36 1.55 1.38 1.07
      (95% CI) (0.90 – 2.27) (1.25 – 2.03) (1.21 – 1.63) (0.81 – 1.41) (0.92 – 2.03) (1.22 1.97) (1.20 – 1.59) (0.82 – 1.39)
      KRAS/LKB1
      All mNSCLC Non-squamous
      IO Chemotherapy IO Chemotherapy
      1L (n = 270) 2L (n = 670) 1L (n =2,137) 2L (n = 863) 1L (n = 187) 2L (n = 498) 1L (n = 1,687) 2L (n = 683)
      KRAS/LKB1, N (%) 17 (6.3) 56 (8.4) 140 (6.6) 42 (4.9) 16 (8.6) 52 (10.4) 133 (7.9) 40 (5.9)
      OS
      Median 303 209 356 343 341 230 363 350
      (IQR) (222 – NA) (72 – 666) (272 – 450) (254 – 554) (130 – NA) (72 – 666) (284 – 462) (254 – 554)
      HR 1.46 1.63 1.55 1.27 1.44 1.78 1.61 1.28
      (95% CI) (0.74 – 2.86) (1.16 2.29) (1.26 – 1.90) (0.87 – 1.84) (0.68 – 3.05) (1.22 – 2.59) (1.29 – 2.00) (0.86 – 1.90)
      PFS
      Median 126 67 136 133 174 68 136 133
      (IQR) (77 – 291) (46 – 91) (112 – 160) (91 – 190) (72 – 295) (47 – 91) (112 – 160) (91 – 190)
      HR 1.34 1.81 1.40 1.08 1.34 1.86 1.44 1.05
      (95% CI) (0.80 – 2.24) (1.35 2.44) (1.16 – 1.68) (0.77 – 1.51) (0.76 – 2.36) (1.35 2.57) (1.19 1.75) (0.74 – 1.50)
      Note: Bold text indicates significant results; reference group for LKB1m is LKB1wt; reference group for KRAS/LKB1 is KRASwt/LKB1wt
      Median OS and PFS and IQRs are expressed in days
      Abbreviations: KRAS mutation/LKB1 loss (KRAS/LKB1), Hazard ratio (HR), Interquartile range (IQR), Confidence interval (CI), Immunotherapy (IO), Overall Survival (OS), Progression-free survival (PFS), Wild type (wt)
      Conclusion

      LKB1m and LKB1/KRAS were associated with numerically worse OS and PFS in the 1L setting, irrespective of treatment, and in IO-treated patients in the 2L setting. Results of this real-world study support previous clinical findings and suggest unique relevance of these mutations in 1L chemotherapy and for 1L and 2L IO.

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