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Lung Cancer: 3 key news from ESMO on atezolizumab (aPD-L1), Osimertinib 7 months extra survival, conflicting view on TMB


Oct. 4, 2019


Lung cancer.

- Interim analysis shows survival advantage for single agent atezolizumab (aPD-L1) over platinum-based chemo as first line treatment for NSCLC with high expression of PD-L1 on tumour (≥50%) or immune (≥10%) cells.  ESMO LBA78

PD-L1/PD-1 inhibitors (CPI) as monotherapy or combined with platinum-based doublet chemo (± bevacizumab) are 1L tx options in metastatic NSCLC, with choice of agent(s) determined by PD-L1 expression. For patients (pts) who may be ineligible for combination therapy, CPI monotherapy remains an attractive tx choice. IMpower110 evaluated atezo as 1L tx in PD-L1–selected pts independent of tumour histology.

The 3 primary efficacy populations included 554 TC1/2/3 or IC1/2/3 WT pts, 328 TC2/3 or IC2/3 WT pts and 205 TC3 or IC3 WT pts. In the TC3 or IC3 WT population, atezo monotherapy improved median OS by 7.1 mo (HR, 0.595; P = 0.0106) vs chemo (Table); median follow-up was 15.7 mo. The safety population comprised 286 pts in Arm A and 263 pts in Arm B. Treatment-related AEs (TRAEs) and Grade 3-4 TRAEs occurred in 60.5% (Arm A) and 85.2% (Arm B), and 12.9% (Arm A) and 44.1% (Arm B), respectively.

At this interim analysis, IMpower110 met the primary OS endpoint with statistically significant and clinically meaningful improvement in the TC3 or IC3 WT population. The safety profile favoured Arm A, with no new or unexpected safety signals seen.



- Osimertinib delivers 7 months extra survival as upfront therapy for EGFR-mutant NSCLC compared with first generation EGFR inhibitors [OS 38.6 versus 31.8 months], it is also better tolerated. Osimertinib is already FDA approved in this setting. ESMO LBA5_PR



- Conflicting views from ESMO on the utility of tumour mutational burden (TMB) to predict response to immunotherapy ESMO LBA79 & LBA80

Higher TMB was associated with response to pembrolizumab monotherapy but not pembro/chemo combination.