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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.

Background: Lenvatinib (18 mg) plus everolimus (5 mg) is approved for patients with advanced renal cell carcinoma (RCC) after one or more prior antiangiogenic therapies. Objective: To assess whether a lower starting dose of lenvatinib has comparable efficacy with improved tolerability for patients with advanced RCC treated with lenvatinib plus everolimus. Design, setting, and participants: A randomized, open-label, phase 2 global trial was conducted in patients with advanced clear cell RCC and disease progression after one prior vascular endothelial growth factor–targeted therapy (prior anti–programmed death-1/programmed death ligand-1 therapy permitted). Intervention: Patients were randomly assigned 1:1 to the 14- or 18-mg lenvatinib starting dose, both in combination with everolimus 5 mg/d. Patients in the 14-mg arm were to be uptitrated to lenvatinib 18 mg at cycle 2, day 1, barring intolerable grade 2 or any grade ≥3 treatment-emergent adverse events (TEAEs) requiring dose reduction occurring in the first 28-d cycle. Outcome measurements and statistical analysis: The primary efficacy endpoint was investigator-assessed objective response rate (ORR) as of week 24 (ORRwk24); the noninferiority threshold of the 14- versus 18-mg arm was p ≤ 0.045. The primary safety endpoint was the proportion of patients with intolerable grade 2 or any grade ≥3 TEAEs within 24 wk of randomization. Results and limitations: The ORRwk24 for the 14-mg arm (32% [95% confidence interval {CI} 25–39]) was not noninferior to the ORRwk24 in the 18-mg arm (35% [95% CI 27–42]; odds ratio: 0.88; 90% CI 0.59–1.32; p = 0.3). The proportion of intolerable grade 2 or any grade ≥3 TEAEs was similar between the two arms (14 mg, 83% vs 18 mg, 80%; p = 0.5). The secondary endpoints of overall ORR, progression-free survival, and overall survival numerically favored the 18-mg arm. A limitation of this study was that the study design did not allow for a full comparison of progression-free survival between treatment arms. Conclusions: The study findings support the approved dosing regimen of lenvatinib 18 mg plus everolimus 5 mg daily for patients with advanced RCC. Patient summary: In this report, we examined two doses of lenvatinib (the approved 18-mg dose and a lower dose of 14 mg) in people with advanced renal cell carcinoma to determine whether the lower dose (which was increased to the approved 18-mg dose after the first treatment cycle) could improve safety without affecting efficacy. The results showed that the efficacy of the lower lenvatinib dose (14 mg) was not the same as that of the approved (18 mg) dose, although safety results were similar, so the approved lenvatinib 18-mg dose should still be used. publishedVersion

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 .

Breast lymphomas comprise a rare group of malignant breast tumors. Among these, a new entity has emerged as a potentially under-diagnosed disease. Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) most often manifests as a late periprosthetic effusion between 1 and 10 years after the implantation of silicone or saline-filled breast prostheses. BI-ALCL is an anaplastic lymphoma kinase-negative T-cell lymphoma that has a distinctively different clinical course than other breast lymphomas or ALCLs. Diagnosis is based on aspiration of the effusion around the implant and CD30 positivity of the sample. Every periprosthetic effusion after breast augmentation or reconstruction using implants should be considered as potential BI-ALCL until proven otherwise. The majority of cases at diagnosis are in the in situ stage, i.e., confined to the lumen around the prosthesis. Most patients have an excellent prognosis when complete removal of the capsule and prosthesis with negative margins is achieved surgically. Some patients, however, develop infiltrative disease with a potentially life-threatening clinical course. Treatment planning regarding the extent of surgery and role of adjuvant therapy, especially in advanced cases, requires further investigation.

Iphosphamide is a chemotherapeutic that is used in the treatment of many cancer types. It causes encephalopathy in as many as 27% of patients. Drug interactions increase the probability of encephalopathy. Aprepitant, which is used in the prevention of chemotherapy-induced nausea and vomitus, is one of the problematic drugs. The treatment of encephalopathy includes discontinuation of iphosphamide, the use of methylene blue and correction of electrolytes. If iphosphamide is still useful, methylene blue can be used prophylactically to prevent encephalopathy.

To evaluate the expression levels of vascular endothelial growth factor receptor-3 (VEGFR3) and CD31 and assess their associations with grade, stage and survival in patients with renal cell cancer (RCC).Our study included 224 consecutive patients who received treatment during the years 1985-1995 in Tampere Finland but had not been treated with modern anti-angiogenesis drugs. All tumor samples were re-classified and investigated using immunohistological techniques. Data were collected from patient records and the Finnish Cancer Registry.In total, 54.2% and 98.2% of the tumor samples tested positive for VEGFR3 and CD31 expression, respectively. CD31 expression levels were classified into two groups according to the median level revealing that its high expression was nearly significantly associated with low tumor stage (p=0.069). In an age- and gender-adjusted analysis, low expression of CD31 associated with poorer survival. Grade 3 and grade 4 tumors had significantly higher mortality rates compared to those of grades 1-2 (hazard ratio (HR)=4.91; 95% confidence interval (CI)=1.12-20.4; p=0.029 for grade 3 and HR=9.31; 95% CI=2.23-38.8; p=0.002 for grade 4). In addition, stage 2, 3 and 4 tumors revealed that they possessed significantly higher mortality hazard ratios compared to those of stage 1 tumors (HR=2.62; 95% CI=1.27-5.41; p=0.009 for stage 2, HR=4.37;95% CI=2.29-8.3; p0.001 for stage 3 and HR 13.8; 95% CI=7.18-26.7; p0.001 for stage 4).High CD31 expression associated significantly with better survival and VEGFR3 had no association with survival. Both higher tumor grade and stage were associated with a decreased survival time.

Claudins are tight junction proteins and their expression is often different in normal and corresponding tumor cells. In the present study, we determined how the expression of claudins 1-5 and 7 correlated to survival, grade and stage of patients with renal cell cancer (RCC).Primary tumor samples were collected retrospectively from 229 RCC patients. Claudins were detected by immunohistochemistry using commercial monoclonal antibodies against claudins 1-5 and 7. Median survival time was 6.5 years confidence interval (CI) (4.5-8.5, n=224). Kaplan-Meier survival estimated method was used in survival analyses.Positive expression was detected in 62%, 67%, 45%, 55%, 7% and 35% of cases for claudins 1, 2, 3, 4, 5 and 7, respectively. High expression of claudin 2 was observed in 20% of cases while high expression of other claudins was less frequent. Claudins were compared to classical prognostic factors. On cross-tabulation, claudin 1 (p0.001) and claudin 2 (p=0.009) were significantly associated with lower-grade and higher-grade tumors, respectively. None of the claudins was significantly associated with tumor stage or patient survival.Claudins 1 and 2 were associated with tumor grade. However, none of the claudins was a more powerful prognostic factor than tumor stage.