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FDA Approves Atezolizumab for Lung Cancer

Jason M. Broderick @jasoncology
Published: Tuesday, Oct 18, 2016

All patients had disease that expressed PD-L1 as measured on tumor cells (TC) and tumor-infiltrating immune cells (IC) by Roche’s investigational IHC test. An IHC score of TC2/3 or IC2/3 was the inclusion criteria established by the trial design.

Atezolizumab was administered at 1200 mg IV at 3-week intervals as frontline therapy to 142 patients (cohort 1), as second-line to 271 patients who had progressed after 1 prior platinum therapy (cohort 2), and to 254 patients who had undergone 2 or more prior chemotherapy regimens (cohort 3).

Overall response rate was the primary endpoint, with secondary outcome measures including duration of response, PFS, OS, and safety.

Among the 659 evaluable patients, the median treatment duration across all cohorts was 4.2 months (range, 0-15). The ORR in cohort 1 was 19% and 17% in cohorts 2 and 3 in patients with TC2/3 or IC2/3 expression. Stronger response was seen in patients with higher expression; ORR rates were 26%, 24%, and 27% in cohorts 1, 2, and 3 in patients with PD-L1 expression of level TC3 or IC3.

At a median follow-up of 8.8, 7.9, and 8.6 months, median OS was 14 months, not reached (NR), and NR, across cohorts 1, 2, and 3, respectively. Six-month OS was achieved by 82%, 76%, and 71% of patients TC2/3 or IC2/3 expression levels in cohorts 1, 2, and 3, respectively, and by 79%, 80%, and 75% of patients in cohorts 1, 2, and 3 having TC3 or IC3 expression levels.

Six-month PFS rates were 46%, 29%, and 31% at the PD-L1 expression level of TC2/3 and IC2/3 and 48%, 34%, and 39% in patients with TC3 or IC3 expression levels in cohorts 1, 2, and 3, respectively.

The safety data for atezolizumab in BIRCH were similar to those observed in other trials. The most commonly reported AEs were fatigue (18%) and nausea (10%). Grade 3/4 treatment-related AEs occurred in 11% of patients overall and 6% of patients discontinued therapy due to a treatment-related AE. All-cause grade 3/4 AEs occurred in 38% of patients.

The phase II POPLAR trial randomized 287 patients with previously treated NSCLC to receive atezolizumab (n = 144) or docetaxel (n = 143). Intravenous atezolizumab was administered at 1200 mg every 3 weeks and docetaxel was used at 75 mg/m2 every 3 weeks.

In the overall study population, the results did not significantly favor atezolizumab; however, as in the BIRCH trial, PD-L1 expression was strongly associated with atezolizumab's efficacy in POPLAR.

In high PD-L1 expressing tumors (TC/IC 3), the median PFS was 7.8 versus 3.9 months, for atezolizumab and docetaxel, respectively (HR, 0.60; 95% CI, 0.31-1.16). The ORR was 38% and 13%, respectively.

In patients without PD-L1 expression (TC/IC 0), a difference was not observed between the 2 groups. Across all expression levels, the ORR was 15% with both treatments. In this group, the median OS was 12.6 and 9.7 months and the median PFS was 2.7 and 3.0 months, for atezolizumab and docetaxel, respectively.

In the study, fewer grade 3 to 5 AEs were experienced by patients treated with atezolizumab compared with docetaxel (44% vs 56%). There was a higher incidence of respiratory side effects with immunotherapy versus chemotherapy. Atezolizumab was associated with aspartate and alanine aminotransferase increases (4% each), colitis (1%), hepatitis (1%), and pneumonitis (2%).

 

References

  1. Barlesi F, Park K, Ciardiello F, et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract for LBA44.
  2. Besse B, Johnson M, Jänne PA, et al. Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC). Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract 16LBA.
  3. Vansteenkiste J, Fehrenbacher L, Spira AI, et al. Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study (POPLAR). Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract 14LBA.
  4. Spira AI, Park K, Mazières J, et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing atezolizumab vs docetaxel in 2L/3L NSCLC (POPLAR). J Clin Oncol. 2015;(suppl; abstr 8010).



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