Quality Of Life In Pts Research Articles

Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: Results from the phase 3 MOTION trial.

11500 Background: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 ( CSF1) gene leading to overproduction of CSF1. TGCT requires a therapy with low toxicity as patients (pts) may need long-term treatment; there is an unmet need for an effective, well-tolerated CSF1 receptor (CSF1R)-targeted therapy that improves functional health and quality of life (QoL). Vimseltinib is an investigational, oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Here we report results from the MOTION trial. Methods: MOTION is a global, phase 3, double-blind study of vimseltinib in pts with symptomatic TGCT not amenable to surgery (NCT05059262). Randomization was 2:1 to vimseltinib 30 mg twice weekly or matching placebo (pbo) for 24 weeks. The primary endpoint was objective response rate (ORR) assessed by blinded independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25. Key secondary endpoints assessed at week 25 were ORR by IRR per tumor volume score (TVS), change from baseline in active range of motion (ROM) of the affected joint and patient-reported outcomes (PROs; PRO Measurement Information System physical function score [PROMIS-PF], worst stiffness numeric rating scale, and EuroQol Visual Analog Scale [EQ-VAS]), and brief pain inventory worst pain response. Safety was also evaluated. Data cutoff was August 22, 2023. Results: Overall, 123 pts were randomized to vimseltinib (n = 83) or pbo (n = 40). Median age was 44 years, 59% of pts were female, and the most common primary disease location was the knee (67%). ORR at week 25 by IRR per RECIST v1.1 and per TVS were significantly higher for vimseltinib vs pbo (RECIST: 40% vs 0%, P < 0.0001; TVS: 67% vs 0%; P < 0.0001). Significant improvements from baseline to week 25 were observed with vimseltinib vs pbo in active ROM (18.4% vs 3.8%; P = 0.0077), physical function (PROMIS-PF: 3.3-point difference between arms, P = 0.0007), worst stiffness (−1.8-point difference, P < 0.0001), and health status (EQ-VAS: 7.4-point difference, P = 0.0155). There were also significantly more pain responders treated with vimseltinib (48% vs 23%; P = 0.0056). Most non-laboratory treatment-emergent adverse events were grade 1/2, and there was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. Conclusions: Patients treated with vimseltinib experienced statistically significant and clinically meaningful improvements in ORR by RECIST v1.1 and by TVS, active ROM, physical function, stiffness, health status, and pain vs pbo. Vimseltinib is an effective, well-tolerated CSF1R-targeted therapy that demonstrates significant clinical benefit and improves functional health and QoL in pts with symptomatic TGCT not amenable to surgery. Clinical trial information: NCT05059262 .

Alliance A022104/NRG-GI010: A randomized phase II trial testing the efficacy of triplet versus doublet chemotherapy to achieve clinical complete response in patients with locally advanced rectal cancer—The Janus Rectal Cancer trial.

TPS3640 Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients (pts) with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated it as a primary endpoint. Collaborating with a multidisciplinary oncology team and pt groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation and improve quality of life for pts. Methods: In this Alliance for Clinical Trials in Oncology randomized phase II trial (1:1), up to 312 pts with microsatellite stable LARC, clinical stage T4N0, any T, N+ or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Pts will be randomized to receive neoadjuvant long course CRT (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks (w) + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Pts will undergo assessment 8-12 w post-TNT completion for the primary endpoint of cCR per previously validated criteria and recommended WW and surveillance if cCR is achieved or TME if an incomplete response is noted. Secondary objectives include time-to event outcomes (disease-free and overall survival, organ preservation time and time to distant metastasis) and adverse effects. Statistical power, based on cCR, incorporates a one-sided alpha = 0.048 and power = 90% yielding 312 patients (156 per arm). Biospecimens including archival tumor tissue, matched / normal blood samples and serial rectal MRI will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and is actively recruiting. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov ID: NCT05610163 Clinical trial information: NCT05610163 .

Real-world treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey.

462 Background: Little is known about treatment and QOL of la/mUC in Saudi Arabia, South Korea, Turkey, and Taiwan. Therefore, this study assessed patient (pt), tumor, and disease characteristics; treatment sequencing; and QOL in pts with la/mUC treated in these countries. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world, multinational, point-in-time study using validated methodology (Anderson et al. Curr Med Res Opin. 2008;24:3063-72) and included physician surveys, chart reviews, and pt questionnaires (Saudi Arabia, Turkey, and Taiwan only). Data were collected (12/2021–3/2022) from oncologists and urologists and adult pts with confirmed la/mUC. EQ-5D visual analogue scale (VAS; scores: 0 [worst health] to 100 [best health]) and the global health status (QL2) from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (scores: 0 [low functioning] to 100 [high functioning]) questionnaires were used to assess QOL. Results: Data were provided by 175 physicians for 988 pts (Turkey, n=300; Saudi Arabia, n=240; South Korea, n=298; Taiwan, n=150) with la/mUC. Mean pt age was 66.3 y; 77% were men. Most (77%) pts had no family history of urothelial carcinoma (UC); 30% recorded no risk factors (eg, genetic risk, smoking, occupational exposure). At initial UC diagnosis, the bladder was the initial tumor location in 82% of pts, of whom 67% had la/mUC, and 83% of pts had an Eastern Cooperative Oncology Group performance status 0–2. At data collection, the most common metastatic sites were the lymph nodes (53%), lungs (29%), liver (27%), and bone (21%). Biomarker/tumor testing was not done in 45% of pts. In pts initially diagnosed with nonmetastatic UC (n=346), 28% received neoadjuvant and 31% received adjuvant therapy. Of pts receiving ≥1 line of therapy (LOT) for la/mUC (n=988), 74% received gemcitabine, 60% received cisplatin, 18% received carboplatin, 17% received a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor, and 4% received best supportive care (BSC) in the first-line (1L) setting; mean duration of therapy (DOT) in 1L was 5.7 mo. Of pts receiving ≥2 LOTs for la/mUC (n=290), 63% received a PD-1/L1 inhibitor and 35% received chemotherapy in the second-line (2L) setting; mean DOT in 2L was 4.9 mo. Of pts receiving ≥3 LOTs for la/mUC (n=87), 59% received chemotherapy (most often cisplatin [46%] or gemcitabine [38%]), 34% received a PD-1/L1 inhibitor, and 10% received BSC only in the third-line (3L) setting; mean DOT in 3L was 4.3 mo. Questionnaires were available for 319 pts. Mean (SD) EQ-5D VAS score was 51.8 (15.6); EORTC QL2 score was 44.6 (19.9). Conclusions: Pts with la/mUC in this multinational study generally received 1L platinum-based and 2L PD-1/L1 inhibitor therapies. These results highlight the need for therapies that improve clinical and QOL outcomes.

S754 Impact of Mirikizumab Treatment on Health-Related Quality of Life in Patients With Crohn’s Disease: A Phase 2 Study Analysis Using the SF-36

Introduction: This analysis evaluated Mirikizumab (miri) effects on Short Form Health Survey (SF-36) in the Phase (Ph)2 randomised, double-blind, parallel, placebo (PBO)-controlled study in patients (pts) with moderately-to-severely active Crohn’s disease (CD). Methods: 12-Week(W) Induction: 191 pts were randomized 2:1:1:2 to 4 treatment arms: intravenous (IV) PBO, 200, 600, or 1000mg miri every 4 weeks (Q4W; W0, 4, and 8). 40-W Maintenance: For miri induction dose, pts achieving ≥1-point improvement in Simple Endoscopic Score for CD (SES-CD) at W12 were re-randomized 1:1 to double-blind maintenance treatment from W12 to W48: continuation of induction IV treatment assignment (IV-IV; N=41) or subcutaneous (SC) 300mg miri Q4W (IV-SC; N=46). Due to small sample sizes, maintenance IV arms and SC arms were pooled. W12 SES-CD non-improvers (N=30) and pts receiving PBO during induction (N=59) received IV 1000mg miri Q4W from W12 to W48. No statistical comparisons were made between miri treatment groups in the maintenance period. SF-36 was assessed at baseline and at W4,12,16, 24, 32, 44, and 52. Results: Statistically significant improvement in MCS was observed at W4 (600mg dose level) and at W12 (all dose levels), whereas statistically significant improvements in PCS were observed only at W12 (600 and 1000mg dose levels) compared to PBO (Table). Though statistical comparisons were not made between treatment groups during maintenance, comparison of mean changes in MCS and PCS suggest that improvements during induction were sustained or further numerically increased with miri maintenance treatment, even in induction SES-CD non-improvers (Table). Conclusion: These data show that miri treatment improves health related quality of life in pts with moderately to severely active CD and suggest an earlier impact on mental compared to physical wellbeing. Maintenance treatment effects were numerically consistent or increased compared to induction effects, even among more refractory pts. These findings will be validated in the ongoing miri Ph3 CD study (NCT03926130). Proinflammatory signals can induce anxiety and depressive symptoms; better understanding of how the effects of anti-inflammatory treatment on the gut-brain axis may improve mental and physical subjective wellbeing requires additional mechanistic studies. Table 1. - Effect of mirikizumab on SF-36 MCS and PCS Change from Baseline Mental Component Score (MCS) Physical Component Score (PCS) Induction Period PBO (N=64) 200 mg IV miri (N=31) 600 mg IV miri (N=32) 1000 mg IV miri (N=64) PBO (N=64) 200 mg IV miri (N=31) 600 mg IV miri (N=32) 1000 mg IV miri (N=64) W0 Baseline (Mean ± SD) 37.0 ± 13.2 35.2 ± 10.2 41.1 ± 10.4 40.4 ± 11.6 38.9 ± 8.3 38.4 ± 6.4 42.9 ± 7.8 39.5 ± 8.6 W4 CFBL (LSM ± SE) 1.9 ± 1.0 2.6 ± 1.4 5.2 ± 1.4* 3.1 ± 1.0 2.4 ± 0.7 3.3 ± 1.0 3.4 ± 1.0 4.2 ± 0.7 W12 CFBL (LSM ± SE) 2.3 ± 1.1 7.5 ± 1.6* 6.5 ± 1.6* 6.1 ± 1.2* 3.1 ± 0.8 4.7 ± 1.1 8.0 ± 1.1** 6.7 ± 0.8** Maintenance Period PBO-1000 mg IV miri (N=59) NI-1000 mg IV miri (N=30) All IV-IV miri (N=41) All IV-SC miri (N=46) PBO-1000 mg IV miri (N=59) NI-1000 mg IV miri (N=30) All IV-IV miri (N=41) All IV-SC miri (N=46) W0 Baseline (Mean ± SD) 37.2 ±13.0 38.0 ±11.2 42.0 ± 10.1 38.7 ±10.7 39.5 ± 8.1 40.8 ± 8.3 41.1 ± 8.5 38.1 ± 7.1 W24 CFBL (Mean ± SD) 7.4 ± 8.7 7.7 ± 11.7 7.0 ± 10.6 5.9 ± 13.1 6.8 ± 7.3 7.1 ± 7.8 9.6 ± 5.6 7.1 ± 8.3 W52 CFBL (Mean ± SD) 7.1 ± 10.6 7.3 ± 9.8 8.5 ± 11.3 11.5 ± 11.4 9.9 ± 7.2 7.1 ± 8.2 10.2 ± 8.7 10.7 ± 7.9 Abbreviations: CFBL = change from baseline; IV = intravenous; IV-IV = pooled maintenance IV treatment arms for patients at each miri induction dose level who achieved ≥1-point improvement in SES-CD at W12 who were re-randomized to continued induction IV treatment assignment during maintenance; IV-SC = pooled maintenance SC treatment arms for patients at each miri induction dose level who achieved ≥1-point improvement in SES-CD at W12 who were re-randomized to SC 300mg miri Q4W during maintenance; LSM = least squares mean; NI = SES-CD non-improver (a patient who received miri during induction who did not achieve a ≥1-point improvement in SES-CD at W12); PBO = placebo; SC = subcutaneous; SD = standard deviation; SE = standard error; W = week. For statistical comparisons across induction treatment groups, a mixed model for repeated measures was used. The model includes treatment, region, prior biologic CD therapy used, baseline, visit and baseline by visit, and treatment by visit.p-values versus PBO: *p< 0.05; ** p≤0.001. Bolded values are statistically different versus PBO.

Impact of trial-eligibility as factor for clinical outcome of patients with renal cell carcinoma treated with first-line pazopanib: Subgroup analysis from the prospective, non-interventional study PAZOREAL.

e16511 Background: In a real-world setting, a substantial number of patients (pts) with metastatic renal cell carcinoma (mRCC) do not meet all eligibility criteria for a clinical trial. Thus, data on effectiveness and safety of 1st-line (1L) treatment with pazopanib (PAZO) as well as quality of life (QoL) is underrepresented for those pts and data on treatment sequences implementing PAZO as 1L are sparse. Methods: PAZOREAL is a prospective, multi-center, non-interventional study to evaluate effectiveness, safety and QoL in pts with mRCC treated with 1L PAZO, and nivolumab (NIVO) or everolimus in second and third line. In this subgroup analysis, the clinical outcome of trial-eligible (TE) and trial-ineligible (TIE) pts with mRCC was assessed by means of overall survival (OS), time on drug (ToD), treatment-emergent adverse events (TEAE) and QoL evaluated by EQ-5D-5L. Pts were rated TIE if they met at least one of the following three ‘TIE criteria’: (i) Karnofsky Performance Status &lt; 70%, (ii) hemoglobin below the lower limit of normal, and (iii) non-clear cell carcinoma1. Results: Of 398 pts treated between December 2015 and February 2021, 376 pts received 1L treatment with PAZO. The median age was 69.7 years. 146 pts were categorized TE and 184 pts TIE, for 46 pts assessment was not applicable. Most of all pts were initially treated with PAZO 800 mg (TE: 71.9% vs TIE: 63.0%). Median ToD for PAZO was 7.7 months (95% CI 6.1-9.0) for TE and 6.0 months (95% CI 4.5-8.1) for TIE. A similar fraction of TE and TIE pts were treated with 2L NIVO (43.8% vs 44.0%). Median OS was 53.2 months (95% CI 38.9-NA) for TE and 26.0 months (95% CI 17.3-35.9) for TIE. The 12-month OS rate was 77.9% for TE and 67.1% for TIE. In patient reported outcome (PRO) measures, baseline QoL was estimated higher for TE than TIE, i.e., 63.2% TE vs 49.2% TIE pts had no limitations for mobility and 82.9% TE vs 61.7% TIE pts were independent in self-care. Frequency of related TEAEs grade 3/4 were comparable for TE and TIE (26.7% vs 25.0%), while TE tended to have less related serious TEAEs (13.0% vs 16.3%). Treatment was discontinued due to related TEAEs in 19.2% of TE and 13.0% of TIE pts. Conclusions: PAZOREAL provides real-world data for mRCC pts usually not represented in clinical trials during the study period. As it was to be expected, median OS and PRO were more favorable for TE than for the TIE pts, reflecting the difference in general condition between these groups. But more importantly, these data underline the tolerability of 1L PAZO treatment even for TIE pts, which is supported by comparable ToD for 1L PAZO and the comparable safety profile in both subgroups.1 Marschner, N. et al. Clin Genitourin Cancer 2017; 15(2):e209-215. doi:10.1016/j.clgc.2016.08.022.

Patient-reported outcomes for the phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.

4070 Background: TOPAZ-1 (NCT03875235) is a randomized, double-blind, global, Phase 3 study evaluating the efficacy and safety of durvalumab (D) in combination with (+) gemcitabine and cisplatin (GC) as first-line treatment for patients (pts) with advanced biliary tract cancer (BTC).1 D + GC significantly improved overall survival (OS) versus placebo (PBO) + GC and represents a new treatment option. Methods: A pre-planned secondary objective of TOPAZ-1 was to assess pt-reported outcomes (PROs) for pts receiving D + GC versus PBO + GC. Pts with BTC were randomized 1:1 to D (1500 mg) or PBO, + G (1000 mg/m2) and C (25 mg/m2), for up to 8 cycles, followed by D or PBO monotherapy until disease progression, unacceptable toxicity, or other discontinuation criteria were met. PROs were assessed with the European Organisation for Research and Treatment of Cancer 30-item Quality of Life (QoL) Questionnaire, EORTC QLQ-C30 (C30), and the BTC 21-item module, EORTC QLQ-BIL21 (BIL21). Time to deterioration (TTD) was the primary assessment of PROs; defined as the time from randomization to the date of the first pre-specified, clinically meaningful deterioration (e.g. disease progression). The PRO analysis set included all pts from the full analysis set who completed a questionnaire. Results: Compliance rates for PROs were high at baseline (&gt;81%) and remained high (majority &gt;70% over 28 cycles) for both treatment groups. Baseline scores were comparable between treatment groups. Addition of D was well tolerated, with no significant difference in TTD in D + GC versus PBO + GC for pt-reported symptoms or functioning using either C30 or BIL21 (Table), or Global Health Status/QoL (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.69–1.12; p=0.279). Conclusions: Addition of D to GC improved OS (Oh D-Y, et al. J Clin Oncol 2022;40(suppl 4). Abs 378) and was well tolerated with no difference in TTD of QoL for pts, supporting D + GC as a new treatment option for pts with BTC. Clinical trial information: NCT03875235. [Table: see text]

Sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): Final results from the phase 3 ASCENT study.

1071 Background: Treatment goals for pts with metastatic breast cancer include extended survival and improved quality of life (QoL). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received FDA approval for pts with mTNBC who received ≥2 prior chemotherapies (at least 1 in the metastatic setting). In the pivotal phase 3 ASCENT study (NCT02574455), SG demonstrated a significant survival benefit over single-agent chemotherapy TPC in the primary analysis population of pts with second line or greater (2L+) mTNBC without known brain metastases at baseline (Bardia A et al. NEJM 2021) and QoL (Loibl S. et al. ESMO 2021). With additional follow up, we present the final data on efficacy, including overall survival (OS), safety, and QoL. Methods: Pts with mTNBC refractory or relapsing after ≥2 prior chemotherapies with at least 1 in the metastatic setting were randomized 1:1 to receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) per RECIST 1.1 by independent review in pts without known brain metastases at baseline. Key secondary endpoints included OS, safety, and health-related QoL. Safety was analyzed in pts who received ≥1 dose of study drug. Results: Of 529 pts enrolled, 468 did not have known brain metastases at baseline (median age: 54 y [range, 27-82]; median prior lines: 4 [range, 2-17]). As of Feb 25, 2021 (final database lock), SG (n = 235) vs TPC (n = 233) significantly improved median PFS (5.6 vs 1.7 mo; HR: 0.39; P&lt; 0.0001) and median OS (12.1 vs 6.7 mo; HR: 0.48; P&lt; 0.0001). The OS rate at 24 months was 22.4% (95% CI, 16.8-28.5) in the SG arm and 5.2% (95% CI, 2.5-9.4) in the TPC arm. In the safety population (n = 482), key treatment-related grade ≥3 adverse events with SG (n = 258) vs TPC (n = 224) were diarrhea (11% vs 0.4%), neutropenia (52% vs 33%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%). There was no grade ≥3 neuropathy and 1 case of grade 3 interstitial lung disease reported with SG. No patient experienced a treatment-related death with SG, and there was 1 treatment-related death with TPC due to neutropenic sepsis. Treatment discontinuations due to AEs were ≤3% in both arms. SG arm showed clinically meaningful and statistically significant improvements than the TPC arm in scores for all five primary focus health-related QoL domains. Conclusions: The analysis based on the final database lock of ASCENT confirms the superior survival outcomes of SG over single-agent chemotherapy, with a manageable safety profile and improvement in QoL for pts with mTNBC in the 2L+ setting. These findings reinforce SG as an effective treatment option for this pt population. Clinical trial information: NCT02574455.

Toxicity and outcomes of BRAF and MEK inhibitor “ramp-up” dosing strategies for patients with melanoma: A real-world institutional experience.

e21600 Background: Combination BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) therapy is a widely accepted treatment option for patients (pts) with BRAF-V600E mutant melanoma. Although effective, these combinations exhibit high rates of adverse events (AEs), with 44% - 66% requiring dose modification or interruption and up to 26% discontinuing due to AEs in the adjuvant setting. Enhanced tolerance to BRAFi/MEKi is expected to improve pts quality of life and potentially enhance clinical outcomes. Clinicians at Roswell Park Comprehensive Cancer Center (RPCCC) have implemented a dose escalation regimen upon initiation of BRAFi/MEKi in efforts to enhance the tolerance of these combinations for pts with BRAF-V600E mutant melanoma in the adjuvant and advanced setting. Here we present a retrospective analysis of the toxicity profiles and outcomes associated with this “ramp-up” approach. Methods: Pts presenting to RPCCC in Buffalo, NY for management of stage III or IV melanoma harboring BRAF-V600E mutations were retrospectively observed from 1/2012 to 12/2020. Pts starting BRAFi/MEKi combinations, regardless of prior lines of therapy, were included unless concurrently receiving immune checkpoint inhibition. The “ramp-up” regimen involves a 25% dose of BRAFi and 50% dose of MEKi, which is gradually increased over 4 weekly intervals until full dose is achieved. Pts started on full-dose BRAFi/MEKi were included as a comparison arm. Observations included 1) demographics, 2) treatment regimens and disruptions, 3) rate and severity of AEs, 4) outcomes including best overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). Results: A total of 88 pts were analyzed (21 and 35 receiving “ramp-up” BRAFi/MEKi in the adjuvant and advanced (unresectable stage III or stage IV) setting, respectively, and 32 received full-dose (non-ramp-up) BRAFi/MEKi in the advanced setting). Demographics were similar except pts in the “ramp-up” cohorts were higher in average age (62.0 vs 56.0, p = 0.032) than pts starting at full-dose. Pts receiving adjuvant BRAFi/MEKi at “ramp-up” dosing exhibited a 4.8% (n = 1) rate of grade 3 or higher (Gr3+) AEs and 33.3% (n = 7) AE-related discontinuation rate (9.9 month average time to discontinuation). In the advanced setting, “ramp-up” vs full-dose treated pts exhibited Gr3+ AE rates of 25.7% (n = 9) vs 43.8% (n = 14; p = 0.197) and AE-related discontinuation rates of 34.4% (n = 12) vs 40.6% (n = 13; p = 0.592), respectively. Trends in overall AEs, ORR, PFS, and OS were similar to historical observations across all groups. Conclusions: This real-world analysis suggests that “ramp-up” incremental dosing of BRAFi/MEKi for pts with melanoma in the adjuvant and advanced setting may improve the tolerance and toxicity profiles of these agents without compromising their clinical efficacy, and may be of particular utility in pts with advanced age.

A Phase I/II Study of Venetoclax in Combination with ASTX727 (cedazuridine/decitabine) in Treatment‐Naïve High‐Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

A Phase I/II Study of Venetoclax in Combination with ASTX727 (cedazuridine/decitabine) in Treatment‐Naïve High‐Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

IBCL-372: Efficacy, Safety, and Patient-Reported Outcomes (PROs) of Treatments for Relapsed/Refractory Follicular Lymphoma (R/R FL) in the Third-Line or Later (3L+) Setting: A Systematic Literature Review (SLR)

Context There is no well-defined standard of care in 3L+ R/R FL. Recently, novel treatments were evaluated in trials or approved by regulators. Objective To conduct an SLR evaluating efficacy, safety, and PROs of treatments for 3L+ R/R FL. Design The SLR included publications prior to November 2020 in MEDLINE, MEDLINE In-Process, Embase, and Cochrane Library databases, with a supplemental gray literature search. Main Outcome Measures Efficacy, safety, and PROs. Results Post-screening of 7,330 records, 73 publications covering 28 studies were identified. Studies identified were characterized by line of treatment and response/survival rates; safety and PROs observed from the studies were described. Seven studies on 3L+ were reported as interventions of interest: anti-CD20 monoclonal antibodies (R: 1), PI3K inhibitors (PI3K: 4), EZH2 inhibitors (EZH2: 1), and chimeric antigen receptor T-cell therapy (CAR-T: 1). Efficacy varied. For R: Overall response rate (ORR) 38%; median duration of response (mDOR) 16.3 months (m). PI3K: ORR 43%–59%; mDOR 7.9–12.2 m; median progression-free survival (mPFS) 8.3–11.2 m. EZH2 for mutant/wild-type: ORR 69%/35%; mDOR 10.9 m/13.0 m; mPFS 13.8 m/11.1 m. CAR-T: ORR 94%; mDOR/mPFS not estimable. The most common adverse events (AEs) for R were grade 1/2 fever, chills, asthenia, and pruritus. PI3K: grade 3/4 treatment-emergent AEs (TEAE) rates were 65%–82% and included diarrhea, pneumonia, pyrexia, hyperglycemia, neutropenia, hypertension, anemia, and thrombocytopenia. Grade 5 events occurred in 6%–8% of patients (pts). EZH2: serious TEAEs occurred in 27%, with the most common events being sepsis, general physical health deterioration, and anemia; no AE-related deaths occurred. CAR-T: grade ≥ 3 AEs in 86% of pts, with the most common events being cytopenia and infection; grade ≥ 3 cytokine release syndrome and neurological events in 6% and 15%, respectively; grade 5 AEs in 2% of pts. Only 2 PI3Ks presented PRO data using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire. Both demonstrated favorable improvements in pts quality of life. Conclusions Despite the availability of novel 3L+ therapies, a high unmet need exists for additional treatment options providing a favorable benefit/risk profile for R/R FL pts. Limited PROs have been reported to date, and more studies characterizing patient outcomes are warranted to better elucidate benefit/risk for novel therapies.

Impact on Quality of Life (QoL) of Patients with Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Under Ibrutinib Treatment: Preliminary Data from a Real World Prospective Project (pilot study)

IntroductionIbrutinib (Ibr), is a first-in-class, orally administered covalent inhibitor of Bruton Tirosine Kinase (BTK). In Argentina, IMBRUVICA™ has recently been approved by ANMAT (Argentinian Regulatory Agency) as first or second-line treatment option for patients (pts) diagnosed with Chronic lymphocytic leukemia (CLL) and as second-line treatment for Mantle cell lymphoma (MCL), as well as CLL pts with a chromosomal deletion of 17p. As there is no available information on the impact of Ibr in QoL measurements in the real-world, outside of a sponsored clinical trial, no preliminary hypothesis can be drawn; but considering evidence from controlled trials it is likely that treatment with Ibr could result in an improvement in QoL. Taking this premise, we suggest a probable benefit on QoL in patients under Ibr of ≥ 20% during the first year of treatment compared to baseline.ObjectivesWe aim to detect an improvement in QoL using patient-reported outcomes. Secondary Objective: To evaluate the effects of Ibr on QoL at different times of treatment. Assess hemoglobin variation during treatment with Ibr.Materials and MethodsAll pts signed informed consent (IC) to perform QoL questionnaires and use of personal data. This study is in accordance with the Helsinki declaration. Exploratory analyzes were performed on the evaluations of the results reported by the pt from the Euro-QOL5D questionnaire (EQ5D) with explicit permission to do so from the copyright holder. Both, the descriptive and visual analogue scale (VAS) were analyzed. This information was used as a quantitative measure of health, as judged by the respondents. EQ5D was completed by patients on months 0, 1, 3, 6 and 12 from the start of treatment. At the same time, doses of Ibr and hemoglobin (Hb) value were recorded.ResultsTwelve pts who started monotherapy with Ibr at our center between January 2016 and February 2017 were included. A total of 11 pts (92%) had a diagnosis of CLL and 1 pt (8%) of MCL. The majority of pts, 8 (67%) were men and median age was 75 years (51-84). The starting dose was 420 mg/d in all cases of CLL and 560 mg/d in MCL. Baseline Hb was 11.1 mg/dl (9.0-14.9). In 9 pts (75%) Ibr was a salvage regimen and in 3 pts (25%) was 1st line therapy. Two pts who had signed IC died before completing QoL evaluation from not related to Ibr causes. The median time of treatment was 12 months (1-18). With the EQ5D VAS evaluation, 90% of the pts reported improvement in their perception of health after the initiation of treatment with Ibr, comparing baseline to 3 and 6 month assessments. None reported worsening of QoL. We observed a modification on the VAS EQ with median improvement of 29% (8-80%) after treatment initiation. Median Hb variation during treatment was: 11.1; 11.2; 11.6; 13 and 13.1mg/dl at 1, 3, 6 and 12 months of treatment, respectively. This means a median Hb improvement of 2gr/dl in the first year of treatment. Interestingly, 2 pts (25%) started treatment with normal values of Hb and also reported QoL improvement. Regarding the different areas of evaluation that comprise the EQ5D, improvements were mainly reported in pain, mobility, daily activities and anxiety.ConclusionsIn this prospective pilot study of QoL assessment with Ibr treatment, we observed that there was an improvement of 29% in this initial sample. This responds positively to the hypothesis raised of an improvement ≥ 20%. Even thought QoL improvement could be partially explained with Hb increase, the Ibr effect on QoL in pts with no baseline anemia is an interesting finding and remains to be determined. We expect to continue with the recruitment of patients by extending the proposal to other centers to reach the sample size needed for statistical confirmation. DisclosuresPavlovsky:Janssen: Honoraria, Speakers Bureau.

The impact of early palliative care on the quality of life of patients with advanced pancreatic cancer: The IMPERATIVE study.

12116 Background: Pancreatic cancer (PDAC) is an aggressive, deadly disease. Chemotherapy (CT) can improve survival by months, but symptom burden is heavy and quality of life (QOL) is poor. Early palliative care (EPC) alongside standard oncologic care improves QOL and survival in other types of cancer; however, the impact on QOL and symptom burden in advanced PDAC is not known. The primary objective of this study was to test for improvement in QOL between baseline (BL) and 16 weeks (wks) among patients receiving EPC. A secondary objective was to test for decreased symptom burden between BL and 16 wk. Methods: In this prospective case-crossover study, patients &gt;18 years with advanced PDAC received EPC provided by a subspecialist palliative care physician and advanced practice nurse plus standard oncologic care. Ambulatory EPC visits occurred every 2 wks for the first month, then every 4 wks until wk 16, and then as needed. The Functional Assessment of Cancer Therapy – hepatobiliary (FACT-hep) and Edmonton Symptom Assessment System (ESAS) questionnaires were completed at enrollment and every 4 wks until wk 16. Least square means and 95% confidence intervals were computed. A generalized linear mixed model was used to test for statistically significant change in scores between BL and wk 16. A sample size of 20 patients provides 80% power after controlling for covariates; 40 patients were enrolled to account for anticipated attrition and missing data. Results: Of 40 patients, 25 (62.5%) were male, 28 (70%) had metastatic disease, 31 (77.5%) had an ECOG performance status of 0-1, 17 (42.5%) had a body mass index (BMI) &gt;25, 35 (89.7%) had an elevated CA19-9 and 31 (77.5%) received CT. Median age was 70.2 (range 63.0-77.5). BL and wk 16 questionnaires were completed by 100% and 70% of patients, respectively. The mean FACT-hep score at BL was 118.8, compared to 125.7 at wk 16, for a mean change of 6.89, [95%CI (-1.69-15.6); p = 0.11]. The mean change from BL to wk 16 for FACT-hep was statistically significant in patients receiving CT, 10.1 [95%CI (0.32-19.8); p = 0.04], patients with metastatic disease, 14.7 [95%CI (5.30-24.1); p = 0.0030] and patients with a BMI &gt;25, 12.5 [95%CI (1.29-23.7); p = 0.03]. The mean ESAS total symptom score at BL was 25.3, compared to 22.7 at wk 16 (p = 0.28). In those with metastatic disease the mean change was statistically significant, -5.73 [95%CI (-11.21 to -0.24); p = 0.04]. Conclusions: EPC resulted in improved QOL in pts with PDAC receiving CT and those with a BMI &gt;25, and improved QOL and symptom burden in patients with metastatic disease. Given minimal attrition and high rates of questionnaire completion, our sample size was robust, resulting in strong power. Providing palliative care alongside standard oncologic care results in clinically meaningful improvements. Access to palliative care, shortly after diagnosis, should be available for patients with advanced PDAC. Clinical trial information: NCT03837132.

Preventive counseling with subsequent remote support does not further improve the quality of life after catheter ablation of atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is associated with substantially reduced quality of life (QoL). Both catheter ablation (CA) and education have a potential to improve QoL in AF patients (pts). Purpose To assess the impact of preventive counseling with long-term support on QoL in pts after CA performed for paroxysmal AF. Methods A prospective randomized controlled study with 2 parallel groups of pts with paroxysmal AF after CA (radiofrequency or cryoablation). Pts were randomized (1:1) into 2 groups. Before discharge, both groups received 1 preventive counseling session with focus on their individual risk factors profile. After discharge pts from intervention group received biweekly preventive counseling via email for 3 months (6 sessions). Control group received usual care. QoL was assessed at baseline and at 12 months using SF-36 questionnaire. Results A total of 90 pts aged 35 to 80 years were enrolled (mean age, 57.4 ± 9.9 years, men, 52.2%). Both groups had a poor QoL at baseline, and both groups experienced improvement in the physical health component at 1 year, but the degree of this improvement in the intervention group was similar to the control (table). Conclusions Preventive counseling with remote support via email does not further improve QoL in AF pts after CA. Intervention group Control group P Integral component of physical health Baseline (points) mean ± SD 44.1 ± 7.9 40.2 ± 8.7 0.028 Mе (25%; 75%) 44.5 (38.7; 50.1) 38.6 (34.4; 47.1) At 12 months (points) mean ± SD 49.4 ± 6.0* 45.7 ± 7.7* 0.010 Ме (25%; 75%) 51.0 (45.2; 53.9) 46.3 (42.4; 50.6) Δ% after 12 months, Ме (25%; 75%) 11.8 (1.4; 32.7) 18.7 (-0.3; 30.4) n/s Integral component of mental health Baseline (points) mean ± SD 46.1 ± 9.0 45.0 ± 8.4 n/s Mе (25%; 75%) 47.8 (39.1; 53.9) 48.0 (37.2; 52.0) At 12 months (points) mean ± SD 48.2 ± 8.1 46.8 ± 8.7 n/s Ме (25%; 75%) 50.1 (46.1; 53.6) 48.0 (41.0; 54.3) Δ% after 12 months, Ме (25%; 75%) 3.6 (-10.8; 32.6) 8.9 (-15.6; 30.8) n/s * p &amp;lt;0.001 vs baseline

Patient Preferences for Maintenance Treatment of Acute Myeloid Leukemia: Results of a Discrete Choice Experiment

Introduction: Standard treatments for older patients (pts) with acute myeloid leukemia (AML) can induce remission; however, responses are often short-lived and survival rates are poor upon relapse (Chen Y, et al. Medicine 2016;95:e4182). To date, no AML maintenance therapies have been approved by the US FDA, but a few have been used 'off-label'. Although some of these maintenance therapies, such as injectable azacitidine (AZA), improved disease-free survival in older pts with AML, overall survival (OS) benefits have been more difficult to achieve. Moreover, injectable therapies are associated with a higher administration burden and infusion reactions, and therefore may not be suitable for long-term maintenance therapy. The randomized, phase 3 QUAZAR AML-001 study (NCT01757535) of CC-486, a novel oral formulation of AZA, was the first maintenance study to demonstrate a significant and clinically meaningful improvement in OS (Wei AH, et al. Blood 2019;134:LBA-3). CC-486 was associated with a 9.9-month increase in OS (vs placebo) with a manageable safety profile and no compromise in health-related quality of life in pts with AML aged ≥ 55 years previously treated with intensive chemotherapy. Although previous research has examined patient preference for induction therapies, very little is known about preferences for AML maintenance therapies. We therefore used an online discrete choice experiment (DCE) survey to determine the relative importance that pts with AML place on key clinical benefits and risks, mode of administration, and out-of-pocket (OOP) costs. Methods: From November 2019 to April 2020, pts aged ≥ 55 years from the USA, Canada, Germany, and Italy who had undergone treatment for AML were invited to participate in an online DCE survey. Attributes in the DCE survey included clinical benefits (time until relapse [6, 12, 24 months] and 2-year survival rate [30%, 50%, 60%]), adverse events (risk of mild-to-moderate stomach problems [40%, 60%, 80%] and risk of serious infection [10%, 20%, 40%]), mode of administration (once-daily oral tablet for 14 or 21 consecutive days/month, subcutaneous [SC] injection in a clinic/hospital for 7 consecutive days/month, or intravenous [IV] infusion in a clinic/hospital for 5 or 7 consecutive days/month), and OOP costs (USD 200, 400, 800). Patient preferences for attribute levels were analyzed using a multinomial logit model and expressed as marginal utilities and maximum acceptable decrease in 2-year survival rate. Results: In total, 170 pts completed DCE surveys (USA, n = 104; Canada, n = 6; Germany, n = 30; and Italy, n = 30). Mean age was 63.0 years, and 54% of pts were male. In all, 73% of pts had achieved remission at any time, 74% had not received prior stem cell transplant, and 79% had been diagnosed with AML in the last 6 months. Based on the DCE survey results, pts valued a 30% increase in the chance of 2-year survival (marginal utility for 60% = 0.84; 95% confidence interval [CI] 0.70-0.99) more than changes in any other attribute. This was followed by a USD 600 decrease in OOP costs (marginal utility for USD 200 = 0.77; 95% CI 0.66-0.89), 18-month increase in time until relapse (marginal utility for 24 months = 0.61, 95% CI 0.48-0.74), an oral tablet for 14 days/month instead of IV infusion 7 days/month (marginal utility = 0.38, 95% CI 0.23-0.54), and a 30% decrease in the risk of serious infection due to injection (marginal utility for 10% = 0.20; 95% CI 0.09-0.32). Risk of mild-to-moderate stomach problems was not important to pts (Figure). Pts preferred an oral tablet taken either 14 or 21 days/month over SC injection 7 days/month (both P = 0.002). In addition, pts were willing to accept a 16% and 14% decrease in the chance of 2-year survival to switch from IV infusion in a clinic/hospital for 7 consecutive days/month to an oral tablet for 14 days/month (95% CI 9.95-22.08) or 21 days/month (95% CI 7.44-20.50), respectively. Conclusions: In this survey of pts with AML, the most important attribute during maintenance therapy was the probability of survival at 2 years. In addition, pts demonstrated a significant preference toward an oral tablet over IV infusions and SC injections in a clinic/hospital, and were willing to accept a significant decrease in treatment efficacy in favor of an oral mode of administration. This study provides valuable insights into patient preferences and may help inform decision-making for AML maintenance therapies. Disclosures Tervonen: Evidera: Current Employment, Current equity holder in publicly-traded company. Seo:Bristol Myers Squibb: Research Funding; Evidera: Current Employment. Nehme:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. La Torre:Bristol Myers Squibb: Current Employment. Prawitz:Bristol Myers Squibb: Research Funding; Evidera: Current Employment. Chen:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Beach:Bristol Myers Squibb: Current Employment. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Systematic Literature Review of the Clinical Efficacy, Safety, and Patient-Reported Outcomes of Treatments in Patients with Relapsed or Refractory Follicular Lymphoma after Two Prior Therapies

Introduction For patients (pts) with relapsed or refractory follicular lymphoma (r/r FL) beyond front-line therapy, there is no well-defined standard of care (SOC) treatment, especially in the third-line or later (3L+) setting. Treatment decisions for symptomatic patients depend on comorbidities, extent of disease, lines of prior therapy and duration of response to initial anti-CD20 containing treatment. Treatment options for 3L+ may include similar options to the ones in earlier lines, with a preference for non-cross-resistant schemes. Recently, a plethora of new compounds are being studied in clinical trials. A systematic literature review (SLR) was conducted to identify relevant evidence on clinical outcomes in pts with r/r FL, including conventional treatments and emerging compounds, within the 3L+ setting. Methods We performed a SLR on March 17, 2020. Clinical trials and observational studies were searched through Embase, PubMed, and Cochrane Central Register of Controlled Clinical Trials from 1998 to 2020, followed by relevant conference proceedings and regulatory documents. Evidence assessing any intervention as 3L+ FL and published in English language was included. If a study included broader indolent non-Hodgkin's lymphoma (iNHL) pts, only FL data was reported; if a study included pts with fewer than 3L+, 3L+ data was included, with mixed line results excluded. Conventional treatments, defined as approved or clinical guideline recommended treatments, included anti-CD20 monoclonal antibody (mAb)-containing regimen, mAb alone, chemotherapy alone, phosphatidylinositol 3-kinase (PI3K) inhibitors (idelalisib, copanlisib, duvelisib), lenalidomide + rituximab (R2), radio-immunotherapy (RIT) with yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, autologous and allogeneic stem cell transplantation (auto- and allo-SCT). Emerging compounds included new treatments that are not approved but were tested in the context of clinical trials (bruton tyrosine kinase inhibitors, bortezomib, polatuzumab vedotin, daratumumab, inotuzumab, bi-specific T-cell engaging CD19 mAb, anti-CD19 chimeric antigen receptor T-cell [CAR-T] therapy). Results Of the 3747 publications identified, 74 studies assessing 26 treatment regimens, including conventional ones like rituximab (R)-containing immunochemotherapy to emerging compounds such as CAR-T therapies, were selected. Across the conventional regimens, 7 studies reported clinical trial data with relatively large 3L+ FL populations (Table 1). With R monotherapy, PI3K inhibitors and tazemetostat, the reported complete response (CR) rates and overall response rates (ORR) ranged from 1-20% and 34-77%, while median duration of response (mDOR) ranged between 7.9-16.3 months. Three clinical trials with PI3K inhibitors reported proportions of pts achieving a response of at least 6 months in duration ranging from 18-30%; median progression-free survival (mPFS) ranging from 8.3-11.2 months. For tazemetostat, mPFS was 11.0 months in EZH2 mutant vs 5.7 months in wild-type FL. With allo-SCT, 2-yr PFS rate was 88% and 57% for pts with CR and PR, respectively. Overall survival (OS) data varied: median overall survival (mOS) was 28-38 months for PI3K inhibitors while mOS was up to 85 months after allo-SCT, despite high non-relapse mortality (NRM) rates with most common causes of death being graft-versus-host disease (GvHD) and infections. Safety profiles were also different across treatments, with most common side effects being hepatotoxicity, diarrhea and infections (PI3K inhibitors) to GvHD (allo-SCT). Three trials presented patient-reported outcomes (PRO) data, all using the Functional Assessment of Cancer Therapy (FACT) questionnaire. Two studies with PI3K inhibitors demonstrated favorable or clinically significant improvement on pts quality of life (QoL), but 1 allo-SCT trial did not show a significant difference between baseline and 2 years post-transplant scores. Conclusion To our knowledge, this is the first SLR focusing on 3L+ treatments of FL. Heterogeneity in study design, patient population, safety profile and reported outcomes make it challenging to identify an optimal treatment regimen for FL in the 3L+ setting. More PRO data are needed considering the important role pt QoL plays in treatment selection. Disclosures Ma: Novartis:Current Employment.Kaur:Novartis:Current Employment.Zhao:Novartis:Current Employment.Zhang:Novartis:Current Employment.Ramos:Novartis:Current Employment.Kumar:Novartis:Current Employment.John:Novartis:Current Employment.Bubuteishvili Pacaud:Novartis:Current Employment.Forcina:Novartis:Current Employment.

Development of the Russian version of quality of life questionnaire in patients with GERD - GERD-HRQL

Development of the Russian version of GERD-HRQL questionnaire to assess symptomatic outcomes of GERD in research and real clinical practice. GERD-HRQL questionnaire (V. Velanovich, USA) consists of 11 items: 10 items for assessment of the most frequent symptoms/problems related with QoL in pts with GERD and 1 item for assessment of patient-reported global satisfaction with health condition. In accordance with international guidelines, the new language version of the tool may be used in research and clinical practice after cross cultural adaptation, linguistic validation and psychometric testing. This paper presents the results of cross-cultural adaptation and linguistic validation of the Russian version of GERD-HRQL. The following steps of linguistic and cultural adaptation of GERD-HRQL for Russia were conducted after the permission from the author of GERD-HRQL was obtained: forward translation with creation of two forward translations of GERD-HRQL in Russian, reconciliation and expert evaluation of translations of GERD-HRQL in Russian and creation of the preliminary version of GERD-HRQL in Russian, back translation, harmonization, creation of the first test-version of GERD-HRQL in Russian, cognitive debriefing and decentering, creation of the second test-version of GERD-HRQL in Russian, final expert evaluation and development of the final test-version of GERD-HRQL in Russian. Satisfactory face validity of the Russian test-version of GERD-HRQL was shown: face validity indices were 0.98, 0.95, 0.92, and 0.97. As the result of translation, cross cultural adaptation and linguistic validation, the Russian version of GERD-HRQL for the use in pts with GERD in Russia was developed. The Russian version of GERD-HRQL may be used in research studies and clinical practice after testing its psychometric properties.

Sequential treatment with pazopanib followed by nivolumab in patients with renal cell carcinoma: Updated interim results of the non-interventional study PAZOREAL.

e17075 Background: Real-world evidence is urgently needed to monitor the translation of new treatment approaches into routine clinical practice as well as to improve cancer treatment and survivorship care. Methods: PAZOREAL is a prospective, multicenter, non-interventional study to evaluate effectiveness, tolerability, safety, and quality of life (QoL) in patients (pts) with advanced or metastatic renal cell carcinoma (mRCC) treated with 1st-line pazopanib (PAZO) followed by 2nd-line nivolumab (NIVO). The primary variable was time on drug (TD) in the respective treatment (Tx) lines. Other endpoints include overall survival (OS), safety and QoL evaluated by EQ-5D-5L. Results: Between December 2015 and September 2017, 414 pts were enrolled and 388 pts started first-line PAZO Tx, 136 pts subsequently received NIVO as second-line Tx. At time of data-cut (30 Sep 2019) median TD was 6.5 months (95%CI 5.7-7.6) for 1st-line PAZO and 4.6 months (95%CI 3.3-6.0) for 2nd-line NIVO. 9.0% of 1st-line PAZO pts and 5.9% of 2nd-line NIVO pts achieved a complete response and disease control rate was 58.0% (95% CI 53.0-62.8) and 44.9% (95% CI 36.8-53.2) for PAZO or NIVO, respectively. Median OS was 32.6 months (95% CI 28.0-38.9) for all pts, 32.6 months (95%CI 28.2-NA) for pts with 2nd-line NIVO and 32.3 months (95%CI 18.8-NA) for pts with other 2nd-line Tx. The most commonly reported treatment emergent AEs were diarrhea (37.2%), nausea (21.7%) and fatigue (19.1%) for PAZO Tx and diarrhea (8.8%), peripheral edema (5.9%) and dyspnea, fatigue, nausea, rash, vomiting (5.1% each) for NIVO. 66 pts (17.1%) discontinued PAZO and 7 pts (5.1%) discontinued NIVO due to related TEAEs. During 1st-line PAZO Tx, mean EQ-5D-5L utility scores initially decreased slightly by time, returned to baseline level and remained stable afterwards. During 2nd-line NIVO Tx the utility scores initially increased by time and remained stable thereafter. Similar tendencies were reported for mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Conclusions: The interim results of the PAZOREAL study confirm favorable clinical trial outcomes, the good benefit-risk profile and the sustained QoL in pts with mRCC in a real-world setting. The sequential treatment with PAZO followed by NIVO is effective and well tolerated. Clinical trial information: NIS-Nr.: 6687.

Multicenter Italian bone metastasis database: First prospective data on breast cancer patients.

e13072 Background: Bone Metastases (BM) are still the main cause of morbidity and morbility in cancer patients because of their complications defined as skeletal-related events (SREs).SREs reduce pts quality of life and are associated with an increasing in social and health costs. At present, data concerning BM are mainly obtained retrospectively from monocentric experiences. Methods: We performed a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 month (m)'s follow-up who were registered in a prospective BM database (BMDB). Detailed information on patients at first diagnosis of BM was recorded in a custom-built software system, updated every 6 m by participating centres and reviewed by the coordinator centre.All pts have signed an informed consent. Results: Since October 2014,618 pts with BM from solid tumors were enrolled of whom 220 have BC as primitive site with a 6 m follow-up. Median age was 62 y (range 26-86). Median Follow up was 34 m (6-149). At enrolment 109 (50%) had only BM and 109 (50%) pts had concomitant visceral and BM. Median time to first BM was 47 m (range 0-312) in Bone only disease and 78.6 m in pts with visceral bone metastases. Disease Free interval (DFI) was different according to BC molecular subtypes and stage. The univariate hazard ratio (HR) for visceral or bone metastasis was higher in luminal B tumors (1.56, 95% confidence interval [CI]:1.1-2.3) (p = 0.002), basal-like (2.50, 95% CI:1.1-6.0) (p = 0.043), and HER2-enriched tumors (1.37, 95% CI:0.78-2.4) (p = 0.273). DFI for pts with stage I disease at diagnosis of primary BC was longer than that for stage III pts (median 67.2 m, 95%CI:53.1-96.1, vs. 58.1 m, 95%CI:41.9-73.4), with a HR of 1.84 (95% CI:1.1-3.0) (p = 0.015) for the stage III group, and 0.98 (95% C.I.:0.6-1.5) (p = 0.930) for the stage II group. During BM disease, 98 pts had at least 1 SREs . Zoledronate was used in 69.1% and Denosumab in 28.3% of cases. First line treatment was hormone-based (n = 105, 50.7%) chemo-based therapy (n = 80, 38.7%) and chemo+ormono based (n = 20, 9.7%). During follow up progression disease occurred in 167 pts. Median progression-free (mPFS) and overall survival calculated from metastatic disease diagnosis (mOS) were 15.1 m (95%CI 12.6-18.4) and 66.8 m (95%CI 52.1-79.2),respectively. Conclusions: This study presents prospective data about a cohort of BC pts enrolled at the first BM occurrence and followed over the time, extrapolated by the multicentric observational BMDB in order to better understed the clinical history of breast cancer and bone metastases.

Comparative quality of life in patients randomized contemporaneously to docetaxel or abiraterone in the STAMPEDE trial.

14 Background: Docetaxel (DOC) and abiraterone (ABI) both improve overall survival (OS) in men with locally advanced or metastatic hormone-sensitive prostate cancer (HSPC) but no head to head trials compare the 2 agents. STAMPEDE, a multi-arm multi-stage platform trial, recruited patients (pts) to treatments including DOC or ABI between Nov-11 and Mar-13. There was no evidence OS differed between DOC or ABI, thus quality of life (QOL) may increasingly inform treatment options. Methods: QOL scores were analysed in pts contemporaneously randomised to receive DOC or ABI, in addition to standard of care treatment. Self-assessment QOL questionnaires EORTC QLQ C30 and PR25 were completed during treatment and follow-up. These analyses focus on average global QOL over the first 2 years after randomisation, using repeated measures analysis, plus cross-sectional analyses at 3, 6, 12 and 24 months. A score difference of ≥4 points was pre-defined as clinically meaningful. Results: 173 men randomised to DOC and 342 men randomised to ABI participated in the QOL sub-study and contributed to this analysis. Baseline characteristics and proportion of missing data were similar between groups. Baseline global QOL scores were similar (mean (sd): DOC 77.8 (20) and ABI 78.0 (19.3)). Average global QOL over 2 years was higher in pts randomised to ABI than DOC, although the difference was statistically significant it did not meet the pre-defined clinical parameter (+3.9, 95%CI 0.6 to 7.1, p=0.021). Cross-sectional analyses showed clinically meaningful superior QOL in the ABI group at 3 and 6 months (+6.6, 95%CI 2.6 to 10.7, p=0.001; +8.0, 95%CI 3.6 to 12.3, p&lt;0.001), but not at 1 or 2 years (+1.3, 95%CI -3.0 to 5.6, p=0.545; +4.5, 95%CI -0.25 to 9.2, p=0.063). An exploratory analysis indicated average QOL for pts with metastatic disease (n=207) was better in the ABI group (+4.44, 95%CI 0.2 to 8.6, p=0.036). Conclusion: Global QOL was significantly higher in the first 2 years of treatment for the ABI group compared to the DOC group, though did not meet the pre-defined clinically meaningful threshold. The majority of difference was seen in the first year of treatment. This should be considered when discussing treatment options with pts. Clinical trial information: NCT00268476.

Abstract P2-12-09: Randomized study to determine the efficacy of Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese breast cancer patients (PTS)

Abstract Background: Adjuvant chemotherapy improves outcomes of pts with early breast cancer, but CINV have been regarded as two of the most disturbing side effects, affecting their quality of life (QoL). In this study, the primary objective was to compare the efficacy of olanzapine in addition to the standard aprepitant-based antiemetic regimen for CINV in pts receiving the 1st cycle of adjuvant AC chemotherapy (adriamycin 60mg/m2 and cyclophosphamide 600mg/m2). The secondary objective was to compare the tolerability and efficacy of such regimen in the 4 cycles of AC. Methods: This is a prospective single center, randomized study. Eligible pts had early stage breast cancer of Chinese ethnicity; they were chemotherapy- naive and treated with adjuvant AC chemotherapy. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomly allocated to Olanzapine (with olanzapine) or Standard (without olanzapine) arms. Individual patient filled in self-reported diary and visual analogue scale for nausea from which information on nausea, vomiting and use of rescue medication were collected; outcomes were compared during acute phase (0-24 hrs), delay (24-120 hrs) and overall time-frame (0-120 hrs) from initiation of AC. QoL was assessed by Functional Living Index-Emesis (FLIE). Results: 120 pts were randomized. For CINV in Cycle 1 AC, outcomes of Olanzapine vs Standard arms were: complete response (acute phase 70.0 vs 51.7%, p=0.0397; delay phase 75.0 vs 45.0%, p=0.0008; overall time-frame 65.0 vs 38.3%, p=0.0035), complete protection (acute phase 70.0 vs 50.0%, p=0.0253; delay phase 71.7 vs 40.0%, p=0.0005; overall 61.7 vs 36.7%, p=0.0062), total control (acute phase 65.0 vs 41.7%, p=0.0104; delay phase 60.0 vs 31.7%, p=0.0018; overall 51.7 vs 26.7%, p=0.0050), ‘no vomiting’ (acute phase 73.3 vs 51.7%, p=0.0142; delay phase 76.7 vs 48.3%, p=0.0013; overall 68.3 vs 40.0%, p=0.0018), ‘no significant nausea’ (acute phase 95.0 vs 75.0%, p=0.0017; delay phase 91.7 vs 65.0%, p=0.0004; overall 91.7 vs 63.3%, p=0.0002),‘no nausea’ (acute phase 76.7 vs 53.3%, p=0.0074; delay phase 65.0 vs 35.0%, p=0.0010; overall 58.3 vs 33.3%, p=0.0060), and need of rescue medication (acute phase 3.3 vs 11.7%, p=0.0654; delay phase 6.7 vs 21.7%, p=0.0133; overall 8.3 vs 23.3%, p=0.0244). Assessment of FLIE on Day 6 after Cycle 1 AC between the Olanzapine vs Standard arms revealed better QOL mean scores for nausea domain (p&amp;lt;0.0001), vomiting domain (p=0.0682) and total scores (p&amp;lt;0.0001). During assessment of multiple cycles, Olanzapine arm was associated with significantly higher rates of complete response in cycle 3 (delay phase and overall time-frame) and cycle 4 (delay phase) as well as total control in cycle 4 (delay phase). Both treatments were generally well tolerated; apart from nausea and vomiting, there was no significant difference in adverse events between the two arms. Conclusions: In this prospective study of Chinese women with breast cancer, the addition of olanzapine to standard antiemetic regimen increases the control of CINV and improves the QoL of pts during AC chemotherapy. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research. Citation Format: Winnie Yeo, Thomas KH Lau, Vicky TC Chan, Li Leung, Dong Lai, Elizabeth Pang, Maggie Cheung, Ashley Wong, Winnie MT Soo, Vanessa TY Yeung, Teresa Tse, Eva WM Yeung, Daisy CM Lam, Kenneth CW Wong, David R Johnson, Kim PK Ng, Herbert Loong, Joyce TY Ng, Florence Mok, Mimi KM Lee, Darren MC Poon, Yvonne SH Yau, Macy Tong, Joyce JS Suen, Frankie KF Mo. Randomized study to determine the efficacy of Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese breast cancer patients (PTS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-09.