Platinum rechallenge versus non-platinum regimens as second-line treatment for advanced thymoma: Analysis of the largest retrospective cohort to date.

Abstract

8117 Background: Although guidelines list platinum-based combination chemotherapy (Pt-rechallenge) as a second-line strategy for patients with thymoma ineligible for curative-intent therapy, evidence is limited to small case series. We investigated the efficacy of Pt-rechallenge versus non-platinum regimens in the largest retrospective cohort of second-line thymoma treatment reported to date. Methods: This multicenter study analyzed patients treated at 39 Japanese institutions. Of 157 patients ineligible for curative-intent therapy who initiated palliative platinum-based chemotherapy (2000–2020), 91 patients receiving second-line systemic cytotoxic chemotherapy were evaluated. Efficacy outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were compared between second-line Pt-containing (Pt-rechallenge) and non-platinum (non-Pt) regimens. Results: Among the 91 patients (median age 59; 91% ECOG PS 0-1) with a median follow-up of 1056 days, 64 (70%) received Pt-rechallenge and 27 received non-Pt regimens (S-1 [tegafur/gimeracil/oteracil], n=15; pemetrexed, n=6; amrubicin, n=5; paclitaxel, n=1). First-line ORR was 51%, and the median chemotherapy-free interval from first-line chemotherapy was 394 days. Pt-rechallenge achieved a significantly higher ORR than non-Pt chemotherapy (40% vs 5%; p=0.0012). Regarding survival outcomes, median PFS was 8.8 months (95% CI, 5.9–11.9) in the Pt-rechallenge group vs 8.0 months (95% CI, 4.8–30.4) in the non-Pt group (HR, 1.29; 95% CI, 0.77–2.18; p=0.325). Median OS was 70.6 months (95% CI, 53.5–82.4) vs 64.4 months (95% CI, 38.7–not estimable) (HR, 1.12; 95% CI, 0.53–2.37; p=0.759); differences in PFS and OS were not statistically significant. In the Pt-rechallenge cohort, outcomes were stratified by anthracycline (A) use in 1st/2nd-line (A→A, n=17; A→non-A, n=28; non-A→A, n=12; non-A→non-A, n=7): ORRs were 50%, 35%, 27%, and 29%; median PFS were 9.3 (95% CI, 4.5–12.2), 6.4 (95% CI, 4.6–10.6), 21.0 (95% CI, 8.7–41.9), and 4.1 (95% CI, 1.8–9.3) months, respectively. Stratified by platinum-free interval (PFI) (<6 months, n=15; 6–12, n=10; 12–36, n=27; ≥36, n=12), ORR were 14%, 63%, 46%, and 20%; median PFS were 5.8 (95% CI, 1.8–19.8), 7.3 (95% CI, 2.1–14.5), 10.3 (95% CI, 5.5–23.5), and 9.0 (95% CI, 3.1–16.9) months. Conclusions: In this largest comparative study to date, platinum rechallenge demonstrated superior response rates compared to non-platinum regimens, particularly in patients with favorable PFI. Study registration: UMIN000048181.