Randomized, double-blind, placebo-controlled, phase II trial of first-line platinum/docetaxel with or without erlotinib (E) in patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCCs).

6017 Background: In a single-arm, phase 2 study, we previously demonstrated that in pts with R/M HNSCC, cisplatin, docetaxel and E improved progression-free survival (PFS) compared to historical data (Kim et al., ASCO 2006). Herein, we evaluated this regimen in a single center, randomized, phase 2 trial. Methods: Pts with R/M HNSCC, with a performance status (PS) 0-2, were randomized (1:1) to receive up to 6 cycles of first-line chemotherapy with cisplatin 75 mg/m2 (or carboplatin AUC 6) and docetaxel 75 mg/m2 i.v. on day 1 every 21 days, plus placebo (P) vs. E 150 mg p.o. daily, followed by maintenance P or E until disease progression. The primary endpoint was PFS. With 120 pts, the study had 80% power to detect an improvement in median PFS from 3.0 to 4.9 months with a two-sided type I error rate of 0.1. Results: From 05/2010 to 07/2015, 120 pts were randomized to the P (N = 60) or E (N = 60) groups. All pts but one initiated treatment and were eligible for evaluation of the primary endpoint – 92 males; median age 62 years; 52 oropharynx, 40 oral cavity, 19 larynx, 8 hypopharynx cancer pts; 86 current/former smokers; 43 with recurrence within 6 months of completion of local treatment; 27 with prior exposure to EGFR inhibitors. Median PFS was 4.4 vs. 6.1 months for the P and E groups, respectively (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.42-0.95 months, p = 0.026). Response rates were 44% vs. 56% for P vs. E (p = 0.21). Median overall survival (OS) for P- and E-treated pts was 13.7 vs. 17.0 months (HR = 0.67, 95% CI 0.43-1.04, p = 0.07). Benefits from E on PFS and OS were more pronounced in pts with oropharyngeal tumors (p≤0.05 for interaction). In the E group, first-cycle rash grade 2-4 (34% pts) was associated with longer OS (HR = 0.40, p = 0.02). E-treated pts experienced a higher incidence of grade 3-4 adverse events (33.9 vs. 53.3%), including diarrhea (3 vs.17%), dehydration (5 vs. 15%), nausea (5 vs. 14%), rash (0 vs. 12%). Conclusions: This study met its primary endpoint. Addition of E to first-line platinum/docetaxel improved PFS and OS. This regimen may warrant further evaluation in randomized, phase 3 trials. Clinical trial information: NCT01064479.

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Axitinib with or without dose titration for first-line metastatic renal cell carcinoma (mRCC): Unblinded results from a randomized phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.lba349 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. LBA349-LBA349 ◽

Cited By ~ 5

Author(s):

Brian I. Rini ◽

Viktor Gruenwald ◽

Mayer N. Fishman ◽

Bohuslav Melichar ◽

Takeshi Ueda ◽

...

Keyword(s):

Drug Exposure ◽

Type I Error ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Dose Titration ◽

Type I ◽

First Line ◽

Antihypertensive Medications ◽

Double Blind

LBA349 Background: Patients receiving the 5-mg twice daily (BID) axitinib starting dose exhibit variable drug exposure; prior pharmacokinetic analyses indicate higher exposure is associated with better outcomes in mRCC. Dose titration based on individual tolerability may optimize exposure and improve efficacy. Methods: Patients (N=213) with treatment-naïve mRCC received axitinib 5 mg BID for a 4-week lead-in period. Then, patients with 2 consecutive weeks of blood pressure ≤150/90 mmHg, no axitinib-related toxicities >grade 2, no dose reductions, and ≤2 antihypertensive medications were randomized (double-blind) to axitinib 5 mg BID + dose titration to 10 mg BID maximum with axitinib or placebo. Those not eligible for randomization continued axitinib 5 mg BID or lower. Primary endpoint was objective response rate (ORR) in randomized arms. Progression-free survival (PFS), overall survival, and safety were secondary endpoints. Assuming response rate under the null hypothesis is 0.15, this study had ≥80% power (1-sided type I error 10%) to detect a ≥25% absolute improvement in ORR with active vs placebo titration. Results: In all, 56 patients each were randomized to active and placebo titration arms, 91 were not randomized, and 10 withdrew during the lead-in period. As of Oct 12, 2012, ORR (95% confidence interval [CI]) was 54% (40–67) in the active titration arm vs 34% (22–48) in the placebo titration arm (1-sided P=0.019), and 59% (49–70) in the non-randomized arm. Median PFS (95% CI) from first dose was 14.5 mo (9.2–24.5) in the active titration arm vs 15.7 mo (8.3–19.4) in the placebo titration arm (hazard ratio favored active titration, 0.85; 95% CI, 0.54–1.35; 1-sided P=0.244), and 16.6 mo (11.2–22.5) in the non-randomized arm. Most frequent all-grade, all-causality adverse events in active titration, placebo titration, and non-randomized arms, respectively, were diarrhea (61% vs 63% vs 63%), hypertension (61% vs 43% vs 82%), and fatigue (45% vs 46% vs 54%). Conclusions: Axitinib is effective and well tolerated in first-line mRCC with prolonged median PFS in all treatment arms compared to historical controls. Axitinib dose titration significantly improved ORR vs placebo. Clinical trial information: NCT00835978.

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Randomized phase 2 study of maintenance pemetrexed (Pem) versus observation (Obs) for patients (pts) with malignant pleural mesothelioma (MPM) without progression after first-line chemotherapy: Cancer and Leukemia Group B (CALGB) 30901 (Alliance).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8517 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8517-8517 ◽

Cited By ~ 2

Author(s):

Arkadiusz Z. Dudek ◽

Xiaofei F. Wang ◽

Lin Gu ◽

Tom Stinchcombe ◽

Robert Arthur Kratzke ◽

...

Keyword(s):

Performance Status ◽

Single Agent ◽

Progression Free Survival ◽

Phase 2 ◽

First Line ◽

Efficacy Analysis ◽

Phase 2 Trial ◽

Group B ◽

Line Chemotherapy ◽

Randomized Phase 2

8517 Background: Standard front-line chemotherapy for advanced MPM is (Pem and a platinum; optimal treatment duration is unknown. We performed a randomized phase 2 trial (NCT01085630) to determine if continuation of single-agent Pem after 4-6 cycles of Pem-platinum would improve progression-free survival (PFS). Methods: Eligible pts had histologically confirmed unresectable MPM, and performance status (PS) 0-1. Pts with at least stable disease following 4-6 cycles of Pem-platinum were stratified by first-line regimen (cis- or carboplatin) and histology (epithelioid versus other) and randomized 1:1 to Obs or continuation of Pem until progression. The primary endpoint was PFS. We assumed that Obs produced a median (m) PFS of 3 months (mo) and Pem would yield a 100% improvement in mPFS to 6 mo; 60 eligible pts (30 per arm) were to be randomized. Results: 72 pts from 30 sites registered 12/10-6/16. The study closed early due to slow accrual once 53 pts were randomized; 49 eligible pts (22 Obs, 27 Pem) are included in the efficacy analysis. Pt characteristics (Obs/Pem): age: median (range) 70 (39-85)/70 (52-87); male 68%/78%; PS 0 27%/33%; epithelioid histology 77%/70%; first-line cisplatin 27%/26%. A median of 4 cycles of Pem (range 1-33) was delivered; 22% of pts required dose modification. mPFS was 3 mo on Obs and 3.4 mo on Pem (hazard ratio (HR) 0.99; 95% CI: 0.51-1.90; p=0.9733). Median overall survival (mOS) was 11.8 mo for Obs, and 16.3 mo for Pem (HR 0.86; 95% CI 0.44-1.71; p=0.6737). Toxicities ≥ grade 3 on Pem included anemia 8%, lymphopenia 8%, neutropenia 4%, and fatigue 4%; there were no grade 5 toxicities. A higher baseline level of serum mesothelin related peptide (SMRP) was associated with worse PFS (HR 1.861, p=0.049). Baseline osteopontin did not significantly affect PFS (p=0.3630). Conclusions: Although it was well tolerated, maintenance Pem following initial Pem/platinum doublet chemotherapy does not improve PFS in MPM patients. High baseline SMRP was associated with shorter PFS. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01085630.

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Randomized phase III trial of imatinib (IM) rechallenge versus placebo (PL) in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): RIGHT study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.18_suppl.lba10502 ◽

2013 ◽

Vol 31 (18_suppl) ◽

pp. LBA10502-LBA10502 ◽

Cited By ~ 4

Author(s):

Yoon-Koo Kang ◽

Min-Hee Ryu ◽

Baek-Yeol Ryoo ◽

Hyun Jin Kim ◽

Jong Jin Lee ◽

...

Keyword(s):

Disease Control ◽

Primary Endpoint ◽

Performance Status ◽

Progression Free Survival ◽

Phase Iii ◽

First Line ◽

Open Label ◽

Ecog Performance Status ◽

Double Blind ◽

Advanced Gist

LBA10502 Background: To palliate and prolong disease control after failure of all available treatment in advanced GIST, resumption of IM dosing has been commonly practiced based on evidence of rapid GIST progression after discontinuation of all TKIs. We evaluated the efficacy of IM rechallenge in pts with advanced GIST following failure of all TKIs. Methods: Eligible pts had metastatic and/or unresectable GIST with prior benefit from first-line IM (defined as disease control for > 6 months), progressive disease (PD) on first-line IM, PD on or intolerance to SU, and ECOG performance status 0-3. Pts were randomized 1:1 to receive best supportive care with either IM 400 mg po once daily or PL. At the time of PD, pts were unblinded and allowed to cross-over to open-label IM. The primary endpoint was progression-free survival (PFS) determined by blinded external radiology review according to RECIST v1.0. Secondary endpoints included overall survival (OS), time to progression, disease control rate (DCR) at 12 weeks, and safety. Results: Between July 2010 and January 2013, 81 pts were randomized (IM: 41, PL: 40) at a single Korean center. All baseline characteristics were balanced between the arms and 40% of pts received ≥ 3 prior TKIs. The planned final analysis in March 2013 demonstrated that the primary endpoint was met, with significantly greater PFS for pts randomized to IM vs. PL : 1.8 vs. 0.9 months, respectively (p=0.002), hazard ratio (HR) 0.45 (95% CI, 0.27-0.76). DCR at 12 weeks was 32% for IM vs. 5% for PL (p=0.003). With 92.5 % of PL pts rapidly crossing over to IM, median OS was 8.2 months for IM vs. 7.5 months for PL (HR of 0.99, p=0.982). The most common treatment-emergent AEs (> grade 3) during double-blind period in the IM arm included anemia (29%), fatigue (10%), and hyperbilirubinemia (7%). Conclusions: Rechallenge of IM significantly improves PFS and DCR in pts with advanced GIST after failure of at least IM and SU, likely by continuous kinase inhibition of the bulk of disease clones which retain IM sensitivity. However, TKI-resistant clones continue to progress leading to relatively brief duration of benefit. Clinical trial information: NCT01151852.

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Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11516 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 11516-11516

Author(s):

Chang Gon Kim ◽

Jin-Hee Ahn ◽

Jeong Eun Kim ◽

Jee Hung Kim ◽

Min Kyung Jeon ◽

...

Keyword(s):

Primary Endpoint ◽

Alternative Hypothesis ◽

Objective Response ◽

Progression Free Survival ◽

Phase 2 ◽

Free Survival ◽

Phase 2 Trial ◽

Previously Treated Patients ◽

Previously Treated ◽

Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

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Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.18_suppl.lba10008 ◽

2012 ◽

Vol 30 (18_suppl) ◽

pp. LBA10008-LBA10008 ◽

Cited By ~ 11

Author(s):

George D. Demetri ◽

Peter Reichardt ◽

Yoon-Koo Kang ◽

Jean-Yves Blay ◽

Heikki Joensuu ◽

...

Keyword(s):

Primary Endpoint ◽

Controlled Trial ◽

Performance Status ◽

Progression Free Survival ◽

Phase Iii ◽

Double Blind Study ◽

Open Label ◽

Ecog Performance Status ◽

Double Blind ◽

Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

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Phase II clinical trial of intravesical bacillus Calmette-Guerin (BCG) followed by sunitinib for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.293 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 293-293 ◽

Cited By ~ 2

Author(s):

Alexander M. Helfand ◽

Cheryl T. Lee ◽

Khaled Hafez ◽

Maha Hussain ◽

Monica Liebert ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Primary Endpoint ◽

Type I Error ◽

Combined Treatment ◽

Progression Free Survival ◽

Complete Response ◽

Type I ◽

Incomplete Response ◽

Hand Foot Syndrome

293 Background: We conducted a phase II trial to evaluate combination therapy with intravesical BCG + sunitinib for prevention of recurrence and progression of NMIBC. Methods: Patients with high-grade clinical ≤ T1N0M0 NMIBC without BCG in the past year were eligible and received induction BCG followed 2 weeks later by 28 days of sunitinib (50mg). The primary endpoint was 3 month complete response (CR) by biopsy and cytology. Patients with incomplete response were eligible for a second cycle of BCG + sunitinib. Secondary endpoints included 2-year recurrence and progression-free survival (RFS, PFS). Toxicity was graded according to the NCI CTCAE v.3.0. The Simon Minimax 2-stage study had 80% power with a 5% type I error assuming a 3m CR of 75% with sunitinib + BCG compared to 55% with BCG alone. If ≥ 25/36 evaluable patients achieved a 3m CR, then the treatment would be considered for further study. Binomial proportions, confidence intervals and Kaplan-Meier estimates are reported. Results: Of 36 evaluable patients, median age was 65.9 years (IQR 59-72). Initial stage was T1 (19), Ta (9), and CIS (8). Thirty-six percent completed sunitinib without interruption. Treatment was delayed (median 12 days (IQR 9-16)) and dose was reduced to 37.5 mg in 13 patients. One patient had reduction to 25mg with re-escalation to 37.5mg. One patient completed a 2nd cycle of BCG + sunitinib for incomplete response. BCG maintenance therapy was given to 21 patients. Of 133 adverse events in 34/36 patients, 6 (4.5%) in 5 patients were ≥ grade 3: thrombocytopenia, diarrhea (2), shingles, extremity rash/pain and hand + foot syndrome. CR at 3m included 26/36 (72%, 95% CI[55,86]) reaching the primary endpoint. The patient who completed a 2nd cycle of BCG induction and sunitinib had CR at 6 months. 2y RFS (patients with intact bladder) was 77% (95% CI[58,88]) and 2y PFS was 100%. Conclusions: The primary endpoint of the study of 25 3m CR has been reached. Combined treatment with BCG + sunitinib is associated with low rates of recurrence and progression. Adverse effects were common and frequent but few were serious. BCG + sunitinib may produce outcomes superior to BCG alone. (Study supported by Pfizer, Inc) Clinical trial information: NCT00794950.

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RECORD-4 phase 2 trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC): Final OS analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.560 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 560-560

Author(s):

Thomas Cosgriff ◽

Lin Yang ◽

Anna Alyasova ◽

Dingwei Ye ◽

Andrey Karpenko ◽

...

Keyword(s):

Disease Progression ◽

Progression Free Survival ◽

Final Analysis ◽

Second Line ◽

Phase 2 ◽

First Line ◽

Primary Analysis ◽

First Line Therapy ◽

Phase 2 Trial ◽

Anti Vegf

560 Background: The phase 2 RECORD-4 study assessed EVE in pts with mRCC who progressed after 1 prior anti-VEGF or cytokine (J Clin Oncol 2015;abstr 4518). At primary analysis, median progression-free survival (PFS, primary end point) in the overall population was 7.8 months (95% CI, 5.7-11.0). Here we present results of the final updated primary PFS and final overall survival (OS) analysis. Methods: RECORD-4 enrolled 134 pts with clear cell mRCC into 1 of 3 cohorts based on prior first-line therapy: sunitinib (cohort 1, n=58), other anti-VEGF (cohort 2, n=62: 23 sorafenib, 16 bevacizumab, 13 pazopanib, 10 other), or cytokines (cohort 3, n=14). Pts received EVE 10 mg/d until progression of disease (PD; RECIST, v1.0) or intolerance. Database lock for final analysis was June 26, 2015. Results: Demographics were balanced among cohorts; overall most pts were men (68%) and most had good/intermediate MSKCC prognosis (90%); median age was 59 yrs. Median duration of exposure was 5.8 mo. At the time of final analysis, study discontinuation was primarily due to disease progression (61%). In the overall population, median PFS (95% CI) was 7.4 (5.6-10.5) mo and median OS (95% CI) was 23.8 (17.0-not evaluable [NE]) mo (Table). Overall rate of grade 3 or 4 adverse events (AEs) was 56%. There were 13 on-treatment deaths; primary causes were disease progression, multi-organ failure, and respiratory failure (2.3% each). Conclusions: RECORD-4 final OS analysis supports EVE as a second-line option after sunitinib and other first-line therapies. EVE safety profile was consistent with previous experience. Clinical trial information: NCT01491672. [Table: see text]

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A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib (REG) in patients (pts) with nonadipocytic soft tissue sarcoma (STS) previously treated with pazopanib (PAZ).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11021 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 11021-11021

Author(s):

Nicolas Penel ◽

Jean-Yves Blay ◽

Jennifer Wallet ◽

Isabelle Laure Ray-Coquard ◽

Axel Le Cesne ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Performance Status ◽

Objective Response ◽

Dose Intensity ◽

Progression Free Survival ◽

Final Analysis ◽

Double Blind ◽

Phase 2 Trial ◽

Previously Treated

11021 Background: After we demonstrated the activity of REG in pts with advanced non-adipocytic STS (MirTLO 2016), we conducted a dedicated study in pts previously treated with PAZ+chemo. Methods: We report here the 5th cohort of a double-blind randomized phase 2 trial (NCT01900743). Pts were treated with regorafenib (160mg/d, 21/28d) or placebo (PB). Pts receiving placebo were offered optional cross-over in case of centrally confirmed disease progression. The primary endpoint was centrally-reviewed RECIST-based progression-free survival (PFS), evaluated on the intent-to-treat dataset. A total of 24 events was required to ensure a 90%-power for HR = 0.33 (median PFS, 3·6 vs 1·2 months), with a 1-sided α = 0·1. Overall survival (OS) was a secondary endpoint. Results: From 12/2015 to 10/2017, 37 pts were randomized (18 REG vs 19 PB) and included in the final analysis. The median age was 60 (36-76). There were 28 women (76%). All pts had a performance status 0 or 1. Histological subtypes included 24 leiomyosarcoma (11 vs 13, in REG and PB, respectively), 1 synovial sarcoma (REG), 12 other sarcoma (7 vs 5). All pts had previously been treated with PAZ +chemo (including doxorubicin: 19 vs 17; ifosfamide: 11 vs 3; trabectedin: 11 vs 9; and dacarbazine: 7 vs 6), with 2-6 prior lines. The median relative dose intensity of REG was 0·86, range 0·41-1. Out of 19 pts assigned to placebo, 13 switched to REG after progression. There was no reported objective response. We observed a significant benefit of REG compared to PB in terms of PFS (HR = 0·38; 95%CI, 0·19-0·76; p = 0·007; median PFS = 2·1 vs 1·1 months, respectively), and OS despite the cross-over (HR = 0·41; 95%CI, 0·17-0·98; p = 0·04; median OS = 18·6 vs 8·2 months). Before cross-over, the most common clinically significant grade 3 or higher adverse events were diarrhea (4 vs 0), dyspnea (3 vs 1), arterial hypertension (2 vs 0), hand-foot skin reaction (2 vs 0). Conclusions: The present study demonstrates that regorafenib has a clinically meaningful anti-tumor activity in pts with non-adipocytic soft tissue sarcoma pretreated by both chemotherapy and pazopanib, improving PFS and OS. Clinical trial information: NCT01900743.

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