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. 2024 Aug 3;24(1):952.
doi: 10.1186/s12885-024-12748-y.

Clinical outcomes for immune checkpoint inhibitors plus chemotherapy in non-small-cell lung cancer patients with uncommon driver gene alterations

Haoyue Qin #  1   2 , Huan Yan #  1   2 , Yangqian Chen  1   2 , Qinqin Xu  3 , Zhe Huang  2 , Wenjuan Jiang  2 , Zhan Wang  2 , Li Deng  2 , Xing Zhang  1   2 , Lin Zhang  4 , Nong Yang  1   2 , Liang Zeng  5 , Yongchang Zhang  6   7   8   9
Affiliations

Clinical outcomes for immune checkpoint inhibitors plus chemotherapy in non-small-cell lung cancer patients with uncommon driver gene alterations

Haoyue Qin et al. BMC Cancer. .

Abstract

Background: Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC.

Methods: We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024.

Results: Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively.

Conclusion: ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.

Keywords: BRAF; ERBB2; Immune checkpoint inhibitor; MET; RET.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the study design
Fig. 2
Fig. 2
Progression-free survival of the study cohort. Kaplan–Meier curves are shown for progression-free survival (PFS) (A, C) and overall survival (OS) (B, D) for each gene alteration group for first-line treatment with immune checkpoint inhibitor (ICI) plus chemotherapy (A, B) for second-line or third-line treatment with ICI-based combination strategy with chemotherapy and/or targeted therapy (C, D). The sequential order of the groups is ERBB2-altered NSCLC, BRAF-altered NSCLC, RET-altered NSCLC, and MET-altered NSCLC
Fig. 3
Fig. 3
Waterfall plots showing the best objective response of each patient harboring ERBB2 alteration (A) BRAF alteration (B) RET rearrangements and MET alterations (C) to first-line treatment with immune checkpoint inhibitor (ICI) plus chemotherapy and second-line or third-line treatment with ICI-based combination strategy with chemotherapy and/or targeted therapy. Each patient’s clinical characteristics were annotated accordingly
Fig. 4
Fig. 4
The bar and pie charts show the percentage of best response to treatment with first-line immune checkpoint inhibitor (ICI) plus chemotherapy and second-line or third-line treatment with ICI-based combination strategy with chemotherapy and/or targeted therapy
See this image and copyright information in PMC

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