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Background Preserving health-related quality of life (HRQOL) is an important goal during renal cell carcinoma treatment. We report HRQOL outcomes from a phase II trial (NCT03173560). Patients and Methods HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of 2 different starting doses of lenvatinib (18 mg vs. 14 mg daily) in combination with everolimus (5 mg daily), following one prior vascular endothelial growth factor–targeted treatment. HRQOL was measured using 3 different instruments—FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L—which were all secondary endpoints. Change from baseline was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale. TTD for each treatment arm was estimated using the Kaplan–Meier method. Results Baseline characteristics of the 343 participants randomly assigned to 18 mg lenvatinib (n = 171) and 14 mg lenvatinib (n = 172) were well balanced. Least-squares mean estimates for change from baseline were favorable for the 18 mg group over the 14 mg group for the FKSI-DRS and most EORTC QLQ-C30 scales, but differences between treatments did not exceed the minimally important thresholds. Median TTD was longer among participants in the 18 mg group than those in the 14 mg group for most scales. Conclusions Participants who received an 18 mg lenvatinib starting dose had favorable HRQOL scores and longer TTD on most scales compared with those who received a 14 mg starting dose.

[No Abstract Available], Merck Sharp Dohme Corp.; Eisai Inc., Woodcliff Lake, NJ, USA, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Eisai Inc., Woodcliff Lake, NJ, USA.

307 Background: LEN 18 mg + EVE 5 mg is approved for advanced RCC following anti-angiogenic therapy. Study 218 was a phase II study evaluating LEN 14 mg vs LEN 18 mg, both in combination with EVE 5 mg, for the treatment of clear cell RCC following treatment with a VEGF-targeted therapy. We have previously reported that the LEN 14 mg arm did not demonstrate noninferiority vs the LEN 18 mg arm for objective response rate (ORR) as of wk 24 by investigator assessment, the primary endpoint of the study. In this exploratory analysis of Study 218 data, we evaluated the efficacy of LEN 14 mg vs LEN 18 mg, both in combination with EVE 5 mg, per IIR assessment and by prior ICI status per investigator assessment. Methods: Pts with measurable clear cell RCC (1 prior VEGF-targeted therapy; prior PD-1/PD-L1 therapy permitted) were randomly assigned 1:1 to LEN 14 mg or 18 mg (starting dose) + EVE 5 mg daily. 115 pts in the LEN 14 mg arm were titrated to LEN 18 mg at cycle 2 as they did not experience intolerable grade 2 or any grade ≥3 TEAEs requiring dose reduction within cycle 1. We analyzed ORR and PFS by IIR per RECIST v1.1; additionally, efficacy endpoints (ORR, PFS, and OS) were analyzed by investigator assessment per RECIST v1.1 by prior ICI status. Results: 311 pts (LEN 14 mg arm, n=156; LEN 18 mg arm, n=155) were included in the efficacy analysis and 341 pts (LEN 14 mg arm, n=173; LEN 18 mg arm, n=168) were included in the summary safety analysis. ORR by IIR (LEN 14 mg arm: 39.7%, 95% CI 32.1–47.4; LEN 18 mg arm: 38.7%, 95% CI 31.0–46.4) was similar between treatment arms. PFS by IIR was numerically longer in the LEN 18 mg arm (median 12.9 mos, 95% CI 9.2–17.1) vs the LEN 14 mg arm (median 11.0 mos, 95% CI 9.3–12.9). OS was numerically longer in the LEN 18 mg arm (median not evaluable [NE], 95% CI 23.8–NE) vs the LEN 14 mg arm (median 27.0 mos, 95% CI 18.3-NE) (previously reported). In 82 pts with prior ICI, for the LEN 14 mg (n=43) vs 18 mg (n=39) arms (95% CI): ORR was 30.2% (17.2–46.1) vs 51.3% (34.8–67.6) by investigator assessment, respectively; median PFS was 12.0 mos (8.9–16.7) vs 12.9 mos (8.4–NE) by investigator assessment, respectively; and median OS was 17.1 mos (10.6–NE) vs 18.0 mos (13.1–NE), respectively. Endpoints were generally numerically improved in the LEN 18 mg arm in pts without prior ICI (data will be presented). As previously reported, the safety profile was similar in both treatment arms: 71.7% of pts in the LEN 14 mg arm and 76.8% of pts in the LEN 18 mg arm had grade 3/4 TEAEs. Conclusions: ORR was similar between treatment arms and PFS was numerically longer in the LEN 18 mg arm per IIR. Efficacy outcomes were generally numerically improved for the LEN 18 mg arm compared with the LEN 14 mg arm, regardless of prior ICI. As previously reported, safety was similar in both treatment arms. These results further support starting pts with RCC at the higher 18 mg dose of LEN + EVE 5 mg. Clinical trial information: NCT03173560 .

314 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer, constituting 80% to 85% of primary renal neoplasms. Preserving health-related quality of life (HRQOL) is an important goal during RCC treatment, but HRQOL analyses in prospective clinical trials in RCC are limited. We report changes in HRQOL, a secondary endpoint of this phase II trial. Methods: HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of two different starting doses of lenvatinib (18 mg vs. 14 mg daily [QD]) in combination with everolimus (5 mg QD), following one prior vascular endothelial growth factor–targeted treatment (NCT03173560). HRQOL was measured using three different instruments, including the FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L. Change from baseline HRQOL was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale (i.e., 10 points for EORTC, 3 points for FKSI-DRS, 0.08 points for EQ-5D index, and 10 points for EQ-VAS). The distribution of TTD and median TTD for each treatment arm were estimated using the Kaplan-Meier method. Results: Baseline characteristics, including baseline scores of the 343 participants randomly assigned to 14 mg QD lenvatinib (n = 172) and 18 mg QD lenvatinib (n = 171), were well balanced. The average scores for the 18 mg QD group were generally higher, with lower symptom severity than the 14 mg QD group. The least squares mean estimates for change from baseline were favorable for the 18 mg QD group over the 14 mg QD group for the FKSI-DRS and most EORTC QLQ-C30 scales; however, the differences between treatments did not exceed the minimally important difference for clinical significance. Both study arms showed an increase diarrhea severity. Median TTD was longer among participants in the 18 mg QD group than those in the 14 mg QD group for most scales. Conclusions: In most scales, participants who received an 18 mg QD lenvatinib starting dose had better HRQOL and longer time to deterioration than those who received a 14 mg QD starting dose. These findings suggest that the approved treatment regimen of an 18 mg starting dose of lenvatinib in combination with everolimus remains favorable for RCC treatment, following one prior vascular endothelial growth factor–targeted treatment. Clinical trial information: NCT03173560 .