Cella, David

PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

349527 Background: Symptoms are common during cancer care but often go undetected. Digital systems that elicit patient-reported outcomes (PRO) surveys may detect symptoms early and prompt clinicians to intervene, thereby alleviating suffering and averting complications. Methods: In a cluster-randomized trial, U.S.-based community oncology practices were randomized 1:1 to digital symptom monitoring with PRO surveys, or to usual care control. Patients receiving systemic treatment for metastatic cancer were eligible. At PRO practices, participants were invited to complete a weekly survey via web or automated telephone system for up to one year, including questions about nine common symptoms, performance status, and falls. Severe or worsening symptoms triggered electronic alerts to care team nurses, and reports showing longitudinal symptom data were available to oncologists at visits. Pre-specified secondary outcomes included impact on physical function, symptom control, and health-related quality of life (HRQL). The primary outcome of survival is not yet mature. Results: At 52 practices, 1,191 patients were eligible and enrolled (593 PRO; 598 control). Clinically meaningful benefits were experienced in physical function by 13.8% more patients with PRO versus control (P=0.009); symptom control by 16.1% (P=0.003); and HRQL by 13.4% (P=0.006). Mean changes from baseline were superior with PRO versus control for physical function (mean difference 2.47, 95% CI 0.41-4.53; P=0.02), symptom control (2.56, 0.95-4.17; P=0.002), and HRQL (2.43, 0.90-3.96; P=0.002). Patients completed 20,565/22,486 (91.5%) of expected weekly PRO surveys. Conclusions: Digital symptom monitoring during cancer treatment confers clinical benefits. Clinical trial information: NCT03249090.

Abstract Background Recurrent pericarditis (RP) patients report that painful, debilitating flares negatively impact their health-related quality of life (HRQoL). RHAPSODY, the Phase 3 trial of rilonacept (IL-1α/IL-1β cytokine trap), included a daily pain diary and patient-reported outcome SF-36v2 to measure HRQoL throughout the trial. Purpose The purpose of this research is to evaluate the effect of rilonacept on HRQoL in relation to changes in pain for RP patients who have a recurrence. Methods RHAPSODY enrolled 86 patients with acute symptomatic RP to receive weekly rilonacept for a 12-week run-in (RI) period and randomized 61 patients (1:1) to receive placebo (n=31) or continue rilonacept (n=30) for the event-driven randomized-withdrawal (RW) period. Patients on placebo who experienced a qualifying recurrence during RW (return of pericarditis pain and increase in C-reactive protein) were rescued with bailout rilonacept. Patients reported daily pericarditis pain electronically, using a 0–10 numeric rating scale (NRS), and completed the SF-36v2 at study visits prior to clinician interaction. Scores from RI Baseline (BL), RI Week 12 (RW BL), Recurrence visit, and RW up to Week 24 (or end of study; EOS) were evaluated for patients who experienced recurrence in RW. Analyses exclude one patient randomized to placebo who had a recurrence after Week 24 of the RW period. Results Analyses focused on the 22 of 30 patients (73%) in the placebo group who experienced a recurrence before Week 24 of RW (median time from RW BL to recurrence: 8.6 weeks). During RI, daily pain scores decreased while on rilonacept (Cohen's effect size [ES] d=−2.0), and SF-36v2 scores improved, with scores at RI BL (Fig. 1 red line) below the general population average of 50 and near or above average at RI Week 12 (Fig. 1 blue line); ES were all large (d&gt;0.8), ranging from 0.917 (Mental Component Summary) to 2.021 (Bodily Pain). At recurrence, pain scores increased (d=6.5; Fig. 2) and SF-36v2 scores were below the population average (Fig. 1 orange line), with largest reductions between RI Week 12 (RW BL) and recurrence for Bodily Pain (−13.4) and Physical Component Summary (−10.6). Following rilonacept bailout, average pain decreased (d=−2.1; Fig. 2), and by RW Week 24/EOS, SF-36v2 scores returned to similar levels as at the end of the RI period (Fig. 1 green line). Conclusion Impaired RI BL SF-36v2 scores indicate negative impact of RP on HRQOL in RP patients. While receiving rilonacept, HRQoL scores improved to near or above population averages, in conjunction with patient-reported pain. After discontinuing rilonacept during RW, HRQoL scores worsened at recurrence and improved upon receipt of bail-out rilonacept, similar to pain. These results provide support for the broader benefit of rilonacept treatment beyond pain, when administered on top of conventional therapies and as mono-therapy, providing evidence of its potential to improve HRQoL in this patient population. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Kiniksa Pharmaceuticals, Ltd.

12102 Background: Allostatic load (AL) conceptualizes the effects of chronic psychosocial adversity on physiologic dysregulation. To date, studies have shown an association between elevated AL and higher disease-specific and overall mortality among cancer patients; however, none have focused on multiple myeloma (MM) patients. We aim to understand the relationship between baseline AL, symptom burden, and mortality among patients enrolled in the E1A11 therapeutic trial in MM. Methods: ECOG-ACRIN E1A11 was a phase III RCT comparing induction with Bortezomib (Arm A) versus Carfilzomib (Arm B) in conjunction with Lenalidomide +Dexamethasone. AL included 7 biomarkers: BMI, alkaline phosphatase, creatinine, C-reactive protein, white blood cell count, albumin and creatinine clearance. AL7 was a composite summary score with a point was assigned for each biomarker value in the highest quartile, except for albumin and creatinine clearance, where a point was assigned for values in the lowest quartile. Endpoints included symptom burden at baseline and ̃1 month, non-completion of induction therapy, and overall survival (OS). Functional Assessment of Cancer Therapy Multiple Myeloma (FACT-MM) items assessed patient-reported symptom burden, including fatigue (item HI7), pain (GP4), and bother by side effects of treatment (GP5) on a 5-point Likert scale. Multivariable logistic regressions assessed the effect of AL7 (ranging 0-7) on high-pain, -fatigue, and -bother (QOL score > = 3 vs < 3), and non-completion of induction therapy. The effect of AL7 on OS was assessed using multivariable Cox regression. Regression covariates included study arm, age, sex, race, ECOG performance status, and the target symptom burden score at baseline. Results: The study cohort included 1087 patients. Mean baseline AL7 was 1.8 (±1.4). In adjusted analysis, a unit increase in AL7 was associated with a greater odds of high pain (OR 1.15, 95%CI [1.04-1.27]) and high fatigue (OR 1.19, 95%CI [1.07-1.32]) at baseline, which did not persist at ̃1 month (pain OR 0.96, 95%CI [0.84-1.10]; fatigue OR 1.03, 95%CI [0.91-1.16]). There was no association between AL7 and high side effect bother at baseline (OR 1.06, 95% CI [0.83-1.35]) or at ̃1 month (OR 1.06, 95%CI [0.90-1.24]). There was no association between AL7 and induction non-completion (OR 1.07, 95%CI [0.96-1.18]). Notably, each unit increase in AL7 was associated with higher mortality (HR 1.26, 95%CI [1.14-1.39]). Conclusions: Despite its association with fatigue and pain at baseline, AL7 was not associated with these symptoms at ̃1 month nor induction non-completion. However, elevated baseline AL7 was associated with poorer OS. AL composite score at baseline, which we interpret as a measure of physiological dysregulation associated with adverse social factors, may have implications on clinical outcomes within clinical trials despite presumed equal treatment access.

TPS4596 Background: There is no standard adjuvant systemic therapy that increases overall survival (OS) over surgery alone for non-metastatic RCC. Anti-PD-1 nivolumab (nivo) improves OS in metastatic RCC and is well tolerated. In mouse models, priming the immune system prior to surgery with anti-PD-1 results in superior OS compared to adjuvant dosing. Remarkable pathologic responses have been seen with neoadjuvant PD-1 in multiple ph 2 studies in bladder, lung and breast cancers. Phase 2 neoadjuvant RCC trials of nivo show preliminary feasibility and safety with no surgical delays. PROSPER RCC seeks to improve clinical outcomes by priming the immune system with neoadjuvant nivo prior to nephrectomy followed by continued immune system engagement with adjuvant blockade in patients (pts) with high risk RCC compared to standard of care surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is accruing pts with clinical stage ≥T2 or TanyN+ RCC of any histology planned for radical or partial nephrectomy. Select oligometastatic disease is permitted if the pt can be rendered ‘no evidence of disease’ within 12 weeks of nephrectomy (≤3 metastases; no brain, bone or liver). In the investigational arm, nivo is administered 480mg IV q4 weeks with 1 dose prior to surgery followed by 9 adjuvant doses. The control arm is nephrectomy followed by standard of care surveillance. There is no placebo. Baseline tumor biopsy is required only in the nivo arm but encouraged in both. Randomized pts are stratified by clinical T stage, node positivity, and M stage. 805 pts provide 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival at 5 years assuming the ASSURE historical control of ̃56% to 70% (HR = 0.70). The study is powered to evaluate a significant increase in OS (HR 0.67). Critical perioperative therapy considerations such as safety, feasibility, and quality of life metrics are integrated. PROSPER RCC embeds a wealth of translational studies to examine the contribution of the baseline immune milieu and neoadjuvant priming with anti-PD-1 on clinical outcomes. As of February 10, 2021, 704 patients have been enrolled (N = 805). Clinical trial information: NCT03055013.

Abstract Background There is a critical need to identify patient characteristics associated with long-term ovarian cancer survival. Methods Quality of life (QOL), measured by the Functional Assessment of Cancer Therapy-Ovarian-Trial Outcome Index (FACT-O-TOI), including physical, functional, and ovarian-specific subscales, was compared between long-term survivors (LTS) (8+ years) and short-term survivors (STS) (&lt;5 years) of GOG 218 at baseline; before cycles 4, 7, 13, 21; and 6 months post-treatment using linear and longitudinal mixed models adjusted for covariates. Adverse events (AEs) were compared between survivor groups at each assessment using generalized linear models. All P values are 2-sided. Results QOL differed statistically significantly between STS (N = 1115) and LTS (N = 260) (P &lt; .001). Baseline FACT-O-TOI and FACT-O-TOI change were independently associated with long-term survival (odds ratio = 1.05, 95% confidence interval = 1.03 to 1.06 and odds ratio = 1.06, 95% confidence interval = 1.05 to 1.07, respectively). A 7-point increase in baseline QOL was associated with a 38.0% increase in probability of LTS, and a 9-point increase in QOL change was associated with a 67.0% increase in odds for LTS. QOL decreased statistically significantly with increasing AE quartiles (cycle 4 quartiles: 0-5 vs 6-8 vs 9-11 vs ≥12 AEs, P = .01; cycle 21 quartiles: 0-2 vs 3 vs 4-5 vs ≥6 AEs, P = .001). Further, LTS reported statistically significantly better QOL compared with STS (P = .03 and P = .01, cycles 4 and 21, respectively), with similar findings across higher AE grades. Conclusions Baseline and longitudinal QOL change scores distinguished LTS vs STS and are robust prognosticators for long-term survival. Results have trial design and supportive care implications, providing meaningful prognostic value in this understudied population.

Abstract Background: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β blocker) to treat RP.Methods: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS Global) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n=16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n=9). All participants received rilonacept weekly for 6 weeks during a base treatment period (TP) plus an optional 18-week extension period (EP). Concomitant medications, including corticosteroids (CS), were tapered, if possible, during EP. HRQoL was assessed using the PROMIS Global, and patient-reported pain and blood levels of c-reactive protein (CRP) were also collected at Baseline and follow-up periods. Results: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline [mean PROMIS Global Physical Health (GPH) and Global Mental Health (GMH), were lower than population norm average]. In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved at EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). Conclusion: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to corticosteroids. Trial Registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522

Introduction: FL is the most common indolent non-Hodgkin lymphoma in the Western world. FL may cause disease-related symptoms, and patients with high-risk disease usually require systemic therapy. BR is commonly used as first-line therapy for high-risk FL, and the addition of bortezomib to a BR backbone has been studied (Evens A et al. Clin Can Res 2020). Little is known about how these therapeutic options impact patients' health-related quality of life (HRQL). To fill this gap, patient-reported outcomes (PROs) were administered to patients enrolled on E2408 to quantify symptom burden and effects of BR versus BVR induction on HRQL. Methods: Patients (n=258) randomized to receive 6 cycles of BR or BVR induction completed PROs assessing neurotoxicity (FACT/GOG-Ntx) at the beginning of each treatment cycle. Additional PROs measuring fatigue (FACT-F), lymphoma-specific concerns (FACT-Lym) and HRQL (Functional Assessment of Cancer Therapy-General; FACT-G) were completed at baseline, mid-treatment (MT; cycle 3/4) and end of induction (EOI; cycle 6). Paired t-test was used to assess PRO score changes from baseline to MT and EOI within BR or BVR group. Two-sample t-test was used to compare change scores between groups at MT and EOI, respectively. Univariate analyses with a linear model identified patient baseline characteristics and clinical factors (age, sex, stage, performance status, # extra nodal sites, FLIPI, GELF, bone marrow involvement, elevated LDH, palpable splenomegaly, B-symptoms, CRIS) associated with PRO change scores from baseline to EOI, adjusting for treatment group. A multivariate model was built with backward variable selection approach for each of the PROs. Results: As shown in Figure 1, compared with baseline, patients randomized to BVR reported significantly worse FACT/GOG-Ntx scores at cycle 4, which continued to end of induction (FACT/GOG-Ntx change scores -2.91 to -3.73; p &lt; 0.001). Neurotoxicity remained stable for patients treated with BR (Ntx change scores -0.02 to -0.55). FACT-Fatigue scores indicated worse fatigue at MT compared to baseline for patients receiving BVR (-2.7, p&lt;0.05), yet they remained stable for BR. FACT-Lym scores were significantly higher at MT (BR: 2.69, p&lt;0.001; BVR: 2.71, p=0.007) and end of induction (BR: 3.32, p&lt;0.001; BVR: 3.55, p&lt;0.001) compared to baseline, signifying a reduction in lymphoma-related symptoms in both arms. FACT-G scores were comparable between treatment arms at each time-point and did not change significantly from baseline to end of induction. Univariate analyses among all patients identified older age and the absence of palpable splenomegaly at baseline as associated with worse FACT-Lym, FACT-Fatigue, and FACT-G change scores, signifying less improvement in lymphoma-related symptoms, fatigue and HRQL from baseline to end of induction (p&lt;0.01). The presence of B-symptoms at baseline was associated with a greater reduction in lymphoma-related symptoms and fatigue from baseline to end of induction (p&lt;0.01). Higher ECOG performance status was only associated with higher FACT-Fatigue change score, suggesting more improvement in fatigue for those with worse performance status at baseline. A multivariate model generated similar results. Conclusions: Despite worse treatment-related symptoms throughout induction, the addition of bortezomib was associated with comparable overall HRQL to those treated with BR. Both treatments were associated with a reduction in lymphoma-related symptoms from baseline to end of induction, likely contributing to stable HRQL throughout treatment despite treatment-related symptoms. Findings also suggest that a subgroup of patients, particularly those who are older, may experience fewer improvements in lymphoma-related symptoms. This underscores the potential need for closer monitoring and clinical management of these patients. Collectively, results are likely to be encouraging for patients experiencing lymphoma-related symptoms, for whom the symptom burden associated with treatment may be worth the trade-off given the potential for improved disease-related symptom control. Disclosures Evens: Merck: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; Epizyme: Consultancy, Honoraria, Research Funding; Mylteni: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding; Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy. Ansell:Trillium: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; AI Therapeutics: Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; ADC Therapeutics: Research Funding. Winter:Norvartis: Consultancy, Other: DSMB; Ariad/Takeda: Consultancy; CVS/Caremark: Consultancy; Delta Fly Pharma: Consultancy; Amgen: Consultancy; Epizyme: Other: DSMB; Merck: Membership on an entity's Board of Directors or advisory committees, Other: advisory board; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: advisory board. Cella:FACIT.org: Membership on an entity's Board of Directors or advisory committees, Other: President; Astellas: Consultancy, Honoraria; Pled Pharma: Research Funding; Janssen: Research Funding; Clovis: Research Funding; Alexion: Research Funding; Apellis: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Kiniksa: Consultancy; IDDI: Consultancy; BMS: Consultancy, Research Funding; ASAHI KASEI PHARMA CORP.: Consultancy; Oncoquest: Consultancy; Mei Pharma: Consultancy; Ipsen: Consultancy, Research Funding; Evidera: Consultancy; DSI: Consultancy, Research Funding; BlueNote: Consultancy; Abbvie: Consultancy, Research Funding; PROMIS Health Org: Membership on an entity's Board of Directors or advisory committees, Other. Kahl:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Acerta: Consultancy, Research Funding. Wagner:Celgene Inc.: Membership on an entity's Board of Directors or advisory committees; Connect Multiple Myeloma Registry: Membership on an entity's Board of Directors or advisory committees.

4627 Background: E4201 compared radiation and gemcitabine (RT+Gem) versus Gem alone in LAPC. The primary endpoint was overall survival; secondary objectives included: objective response rate (RR), progression-free survival (PFS), toxicity and QOL. We previously reported that RT+Gem was associated with improved overall survival compared with Gem alone [median survival time, 11 months and 9.2 months, respectively; p=0.034], without impact in RR or PFS. (ASCO 2008, abstract # 4506). We now report on QOL as measured by the Hep subscale from the FACT-Hepatobiliary [FACT-Hep] between both arms. Methods: Eligible patients had LAPC adenocarcinoma, PS <2, without prior therapy. They were randomized to Arm A: Gem alone (1,000 mg/m2/week x 3, every 4 weeks, 7 cycles), or Arm B: RT (50.4Gy/28 fractions) plus Gem (600 mg/m2/weekly x 6) followed by 5 cycles of Gem alone (1,000 mg/m2/weekly x 3 every 4 wks). The FACT-Hep was administered at baseline (before starting induction), 6 weeks (immediately after completing induction), week 16 (Arm A) or week 15 (Arm B) mid-consolidation, and at 9 months. Results: From April, 2003 to December, 2005, 74 patients were enrolled, 71 were eligible [37 Arm A; 34 Arm B]. Grade ≥3 was reported in 80% and 82.4% in ARM A and B, respectively (p=1.00). Grade IV toxicities, mainly gastrointestinal and hematologic, were more common in ARM B (41.2% vs 5.7%, p=<0.0001). QOL compliance declined over time, most commonly attributable to either patients or staff choosing not to complete or administer the instrument due to declining health (96%, 69%, 60%, and 40% at baseline, week 6, 15/16 weeks and 9 months, respectively). Within Arm B, QoL scores dropped significantly from baseline to 6 weeks. By week 15, QoL scores for patients on Arm B rebounded to levels similar to baseline. Two-sided Wilcoxon rank sum tests failed to suggest differences in median FACT-Hep subscale score between treatment arms at any of the four time-points (alpha = 0.10). Conclusions: RT+Gem is associated with an overall survival benefit without apparent long term adverse impact on QOL when compared with Gem alone. No significant financial relationships to disclose.

LBA2 Background: About 6% of newly diagnosed breast cancer patients present with Stage IV disease and an intact primary tumor (IPT). Locoregional treatment (LRT) for the IPT is hypothesized to improve survival based on retrospective analyses, but randomized trials have provided conflicting data. We now report the results of E2108, a Phase 3 trial that examined the worth of LRT for the IPT following initial systemic therapy. Methods: Stage IV patients with IPT were registered, treated with optimal systemic therapy (OST) based on patient and tumor characteristics; those who did not progress during 4-8 months of OST were randomized to LRT for the IPT, or no LRT. The primary endpoint was overall survival (OS), with locoregional disease control as a secondary endpoint. Stratified log rank test and Cox proportional hazard model were used to compare OS between treatment groups. Cumulative incidence of locoregional recurrence/progression was estimated and Gray test was used for treatment group comparisons. The trial was designed to detect an improvement in 3 year OS rate from 30% with OST alone to 49.3% for OST+LRT (power 95%, 1-sided alpha 0.05) with full information expected after 152 deaths; the data monitoring committee recommended data release after 80% of full information. Results: 390 patients were enrolled between 2/8/11 and 7/23/15, and received OST. Of these, 256 eligible patients were randomized to either continued OST alone (N = 131) or OST+LRT (N = 125).There were 121 deaths and 43 locoregional progression events after a median follow up 59 months (range: 0-91). There was no significant difference in OS (3-year OS rate 68.4% in OST+LRT vs. 67.9% OST alone arm, stratified log-rank p = 0.63, HR = 1.09, 90% CI: 0.80, 1.49) or in progression-free survival (p = 0.40). The locoregional recurrence/progression was significantly higher in the OST alone arm (3-year rate 25.6% vs 10.2%, Gray test p = 0.003). Health-related quality of life (HRQOL) measured by FACT-B Trial Outcome Index was significantly worse in the OST+LRT arm than OST alone arm at 18 months post randomization (60% completion, Wilcoxon rank sum test p = 0.01), but no difference was observed at time points 6 months (74% completion) or 30 months (56% completion). Conclusions: Early local therapy does not improve survival in patients with de novo metastatic breast cancer and an IPT. Although there was a 2.5-fold higher risk of local disease progression without LRT, LRT of the IPT did not lead to improved HRQOL. Clinical trial information: NCT01242800 .