Efficacy of first‐line treatment options beyond RET‐TKIs in advanced RET‐rearranged non‐small cell lung cancer: A multi‐center real‐world study

Abstract

BackgroundAlthough RET‐tyrosine kinase inhibitors (RET‐TKIs) are the preferred first‐line therapy for advanced RET‐arranged NSCLC, most patients cannot afford them. In this population, bevacizumab, immunotherapy, and chemotherapy are the most commonly used regimens. However, the optimal scheme beyond RET‐TKIs has not been defined in the first‐line setting.MethodsThis retrospective study included 86 stage IV NSCLC patients harboring RET rearrangement from six cancer centers between May 2017 and October 2022. RET‐TKIs, chemotherapy, or one of the combination therapies (including immune checkpoint inhibitor (ICI) combined with chemotherapy (I + C), bevacizumab combined with chemotherapy (B + C), ICI and bevacizumab combined with chemotherapy (I + B + C)), were used as the first‐line therapeutics. The clinical outcomes and safety were evaluated.ResultsFourteen of the 86 patients received RET‐TKIs, 57 received combination therapies, and 15 received chemotherapy alone. Their medium PFS (mPFS) were 16.92 months (95% CI: 5.9–27.9 months), 8.7 months (95% CI: 6.5–11.0 months), and 5.55 months (95% CI: 2.4–8.7 months) respectively. Among all the combination schemes, B + C (p = 0.007) or I + B + C (p = 0.025) gave beneficial PFS compared with chemotherapy, while I + C treatment (p = 0.169) generated comparable PFS with chemotherapy. In addition, I + B + C treatment had a numerically longer mPFS (12.21 months) compared with B + C (8.74 months) or I + C (7.89 months) schemes. In terms of safety, I + B + C treatment led to the highest frequency of hematological toxicity (50%) and vomiting (75%), but no ≥G3 adverse effect was observed.ConclusionsI + B + C might be a preferred option beyond RET‐TKIs in the first‐line therapy of RET‐arranged NSCLC. Combination with Bevacizumab rather than with ICIs offered favorable survival compared with chemotherapy alone.