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Atezolizumab/Bevacizumab Combo Shows Potential in EGFR-Mutant NSCLC

Samantha Hitchcock
Published Online:5:32 PM, Fri January 25, 2019

Tony Mok, MD

Both overall survival (OS) and progression-free survival (PFS) were improved in patients with EGFR-mutant nonsquamous cell lung cancer (NSCLC) who were treated with the combination of atezolizumab (Tecentriq), bevacizumab (Avastin), and chemotherapy compared with bevacizumab plus chemotherapy, according to an exploratory analysis of the IMpower150 study.1 These findings were presented at the European Society for Medical Oncology 2018 Asia Congress.

“Adding atezolizumab to standard-of-care bevacizumab and chemotherapy increased OS and PFS benefit across the examined EGFR patient subgroups,” said Tony Mok, MD, the Li Shu Fan Medical Foundation Professor of Clinical Oncology at the Chinese University of Hong Kong, when presenting the findings. “Therefore, this combination treatment may represent a potential new option in EGFR-mutant patients.”

As of a data cutoff of January 22, 2018, the investigator-assessed median OS in the population of patients with EGFR-mutant tumors had not yet been reached (95% CI, 17.0-not estimable [NE]) with the addition of PD-L1 inhibitor atezolizumab (n = 34) compared with 18.7 months (95% CI, 13.4-NE) for bevacizumab plus chemotherapy alone (n = 45).

In addition, there was an increase in PFS with the addition of atezolizumab in the EGFR-mutant population. Median PFS for patients who received the combination of atezolizumab, bevacizumab, and chemotherapy was 10.2 months (95% CI, 7.9-15.2) compared with only 6.9 months (95% CI, 5.7-8.5) with bevacizumab and chemotherapy alone.

The phase III IMpower150 trial randomized equally 1202 chemotherapy-naïve patients with stage IV or recurrent metastatic nonsquamous NSCLC to receive atezolizumab, carboplatin, and paclitaxel (arm A; n = 349), atezolizumab plus bevacizumab and chemotherapy (arm B; n = 359), or bevacizumab and chemotherapy (arm C; n = 337).2

In the investigational arms, atezolizumab was administered at 1200 mg intravenously every 3 weeks and bevacizumab was administered at 15 mg/kg. In each arm, carboplatin and paclitaxel were given on day 1 of each cycle for 4 to 6 cycles. In arm A, maintenance therapy was given with atezolizumab alone and in arm B patients received maintenance therapy with the combination of bevacizumab and atezolizumab. In arm C, maintenance was given with bevacizumab alone.

The study was only designed to compare arms B and C as part of the interim analysis. In addition to the co-primary endpoints of OS and PFS, the study also assessed objective response rates (ORRs) and safety in the intention-to-treat (ITT), wild-type population. Patients who were EGFR-mutant or had an ALK rearrangement were excluded from the interim analysis.

In the exploratory analysis, a high overall response rate (ORR) was also observed in patients with EGFR-mutant tumors. The ORR for arm B was 71% compared with only 42% for arm C. “The addition of bevacizumab to atezolizumab and chemotherapy almost doubled the ORR in EGFR-mutant patients,” Mok concluded.

The duration of response (DOR) was more than doubled with the addition of atezolizumab in arm B. The median DOR was 11.1 months (range, 2.8-18.0) with atezolizumab versus 4.7 months (range, 2.6-13.5) without.

Of the 124 patients who were EGFR-positive, 91 had a sensitizing EGFR mutation and 77 received prior tyrosine kinase inhibitor (TKI) therapy. The addition of atezolizumab to bevacizumab and chemotherapy increased OS benefit across both EGFR-mutant patient subgroups.

The baseline characteristics and safety profile for the EGFR-mutant subgroup were comparable to the overall ITT population in the study. Although 100% of the EGFR-mutant subgroup in arm B experienced treatment-related adverse events (TRAEs), serious events occurred in only 12 patients (36%). Comparatively, 96% of patients with EGFR-mutant tumors in arm C experienced TRAEs, including 9 (21%) patients who experienced serious events.

During his presentation, Mok noted that the percentage of AEs leading to withdrawal from any treatment was slightly higher in arm B with the addition of atezolizumab compared to arm C for patients with EGFR-mutant NSCLC (33% versus 16%, respectively).

Based on findings from IMpower150, atezolizumab in combination with bevacizumab, carboplatin, and paclitaxel was approved in the frontline setting for the treatment of patients with metastatic nonsquamous NSCLC, however, the indication excluded patients with EGFR/ALK aberrations. The exploratory analysis of the phase III trial is the first to show benefit from a checkpoint inhibitor in patients with EGFR-mutant tumors and further studies are currently ongoing to expand the indication.
 
 
References:
  1. Mok TS, Socinski MA, Reck M, et al. IMpower 150: an exploratory analysis of efficacy outcomes in patients with EGFR mutations. Annals of Oncology. 2018;29(abstr; suppl 9): ix173-ix78. doi: 10.1093/annonc/mdy483.
  2. Socinski M, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. doi: 10.1056/NEJMo1716948.


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