3134 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing has been reimbursed in Japan since 2019. However, only 8.2% of patients (pts) had received molecularly-matched treatments. One major reason for this limited drug accessibility is that CGP is covered only after progression with standard of care (SoC). We previously reported that first-line CGP using FoundationOne CDx in advanced solid tumors (FIRST-Dx study) could identify molecular-based recommended therapy (MBRT) for 61% of pts (105/172), and 22.7% (39/172) could be treated by MBRT (JAMA Netw Open 2023, Cancer Sci 2025). To evaluate the impact of the first-line CGP test on survival outcomes, a 3-year follow-up analysis was conducted. Methods: The FIRST-Dx study was a multi-institutional prospective study in Japan. A total of 172 chemotherapy-naïve adult pts with advanced solid tumors (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were registered. This follow-up study was planned for 3 years after the final patient enrollment. The primary endpoint was overall survival (OS). Secondary endpoints were the proportion of pts receiving MBRT, overall response rate, progression-free survival (PFS), and PFS ratio (PFS on MBRT/PFS on prior therapy). Results: Median follow-up period was 25.0 months (0.5–45.2). Forty-six pts (26.7%) received MBRT. The number of pts treated with MBRT was 21 in the 1st-line, 22 in the 2nd-line, 6 in the 3rd-line, and 6 in the 4th-line or later setting. Median OS was significantly longer in pts treated with MBRT (not reached) than in those who did not receive MBRT (26.2 months, HR 0.62 95% CI: 0.39–0.99, log-rank p=0.047). PFS and response rates were shown in Table. Among pts who received 2nd-line MBRT (N=15), the median PFS ratio (PFS on MBRT in 2nd-line/PFS on 1st-line therapy), was 1.2 (range: 0.4–14.6), and 7 pts (47%) achieved a PFS ratio of >1.3, indicating a clinically meaningful benefit of the first-line CGP based MBRT. In an exploratory analysis, propensity score matching (age, sex, cancer type) was performed between pts registered in this study and concurrent real-world pts who did not undergo the first-line CGP, resulting in 67 pts per group. Median OS was significantly longer in the FIRST-Dx group than in the real-world group (23.5 months vs 13.4 months, HR 0.61 95% CI: 0.40–0.94, log-rank p=0.02). Conclusions: MBRT identified by CGP in the first-line setting improved access to targeted therapies and was associated with superior survival outcomes than SoC in advanced solid tumors. Our data suggest that CGP in Japan should be available prior to SoC initiation. Clinical trial information: jRCT1050220041. Median progression-free survival and response rate. MBRT SoC p-value Median PFS (months) 1st-line 13.7 11.3 0.04 2nd-line 11.0 5.6 <0.01 Response Rate (%) 1st-line 52.4 37.8 0.24 2nd-line 45.5 13.2 <0.01
Ikeda et al. (Wed,) studied this question.