Abstract 1387P
Background
HER2 alterations are identified in 2-4% of non-small cell lung cancer (NSCLC), indicating poor clinical outcomes. Due to the deficiency of effective targeted therapies in the first-line setting, chemotherapy alone or combined with Bevacizumab, immune checkpoint inhibitors (ICIs) or both are recommended as standard options. However, the optimal therapy is still undetermined.
Methods
Stage IV NSCLC patients with HER2 alteration were retrospectively analyzed from 6 cancer centers in China between May 2017 and February 2023. All the patients received chemotherapy alone (C), chemotherapy combined with Bevacizumab (BC), chemotherapy combined with ICIs (IC), or chemotherapy combined with Bevacizumab and ICIs (IBC) as first-line strategies. The clinical outcomes were evaluated.
Results
Eighty patients with HER2 mutation (75/80) or amplification (5/80) were included, in which 10 patients received chemotherapy alone, 37 received BC, 24 received IC, and 9 received IBC treatment. Compared with chemotherapy, combination therapy significantly improved mPFS (8.47 months VS 4.97 months, p<0.0001). Further analysis based on different combination mode showed that, each of the combination therapeutics, including BC (mPFS 7.27 m, HR=0.31, 95% CI: 0.14-0.68, p<0.001), IC (mPFS 8.47m, HR=0.20, 95% CI:0.08-0.48, p=0.004) and IBC (mPFS 16.3m, HR=0.08, 95% CI: 0.02-0.25, p<0.001), gave beneficial PFS compared with chemotherapy. In our effort to determine the optimal combination strategy, we found IBC treatment gave longer mPFS compared with BC (HR=0.15, 95% CI: 0.04-0.50, p<0.001) and IC (HR=0.43, 95% CI: 0.16-1.18, p=0.092). However, the efficacy of IC and BC schemes are comparable. Table: 1387P
| Groups | Patient number | ORR, % (95% CI) | DCR, % (95% CI) | mPFS, months (95% CI) |
| Chemotherapy | n=10 | 30.0(1.60,58.4) | 100(100,100) | 4.97 (4.09, 5.84) |
| Combination | n=70 | 25.7(15.5,36.0) | 91.4(84.9,98.0) | 8.47 (7.28, 9.35) |
| IC | n=24 | 29.2(11.0,47.4) | 87.5(74.3,101) | 8.47 (7.15, 9.78) |
| BC | n=37 | 18.9(6.30,31.5) | 91.9(83.1,101) | 7.27 (6.27, 8.26) |
| IBC | n=9 | 44.4(12.0,76.9) | 100(100,100) | 16.3 (8.83, 23.8) |
| ALL | n=80 | 26.3(16.6,35.9) | 92.5(86.7,98.3) | 7.63 (6.35, 8.92) |
Conclusions
Chemotherapy-based combination strategies improve patient survival compared with chemotherapy in the first-line therapy of HER2-altered NSCLC, while the IBC mode lead to the optimal PFS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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