- Efficacy data from the IMpower132 phase 3 randomized trial have demonstrated the survival benefit of atezolizumab added to chemotherapy regimens of pemetrexed+carboplatin or cisplatin for advanced nonsquamous NSCLC.
Why this matters
- An earlier interim analysis of the IMpower132 clinical trial (NCT02657434) met its coprimary endpoint of PFS.
- The combination of atezolizumab plus chemotherapy with pemetrexed along with cisplatin or carboplatin reduced the risk for disease worsening or death compared with chemotherapy alone in the first-line treatment of advanced nonsquamous NSCLC.
- Whether the benefits persist and whether the treatment is safe have been unclear.
- Phase 3 randomized trial evaluating first-line pemetrexed+carboplatin or cisplatin±atezolizumab in patients with stage IV nonsquamous NSCLC without EGFR or ALK driver mutations.
- 578 patients randomly assigned 1:1 to receive 4 or 6 cycles of carboplatin area under the curve 6 mg/mL/minute or cisplatin 75 mg/m2+pemetrexed 500 mg/m2 every 3 weeks (Q3W) alone (arm PP, n=286) or in combination with atezolizumab 1200 mg Q3W (arm APP, n=292).
- Maintenance phase with pemetrexed (arm PP) or atezolizumab+pemetrexed (arm APP).
- Coprimary endpoints of PFS and OS (interim analysis).
- Baseline characteristics in the 2 groups were comparable for median age, sex, race, Eastern Cooperative Oncology Group Performance Status, smoking status, liver metastasis, prevalence of programmed death-ligand 1 (PD-L1) expression, use of carboplatin, and number of chemotherapy cycles.
- PFS significantly improved in arm APP vs arm PP (7.6 [95% CI, 6.6-8.5] months vs 5.2 [95% CI, 4.3-5.6] months; HR, 0.60 [95% CI, 0.49-0.72]; P<.0001>
- Interim OS favored the atezolizumab group (18.1 [95% CI, 13.0-not reached] months) vs arm PP (13.6 [95% CI, 11.4-15.5] months).
- Exploratory analysis revealed the benefit of atezolizumab in patients with high expression of PD-L1.
- All-cause adverse events and treatment-emergent adverse events were more frequent in the atezolizumab group, as expected, with no new safety signals detected.
- "IMpower132 met its coprimary endpoints of investigator-assessed PFS in the intent-to-treat population. Atezolizumab+pemetrexed+carboplatin or cisplatin has a manageable safety profile consistent with known safety risk of the individual therapies. OS data showed a numerical improvement of 4.5 months at this interim analysis. The final analysis is anticipated in the first half of 2019," said presenter Vassiliki A. Papadimitrakopoulou, MD, The University of Texas MD Anderson Cancer Center, Houston.