The Management of Oligoprogression in the Landscape of New Therapies for Metastatic Melanoma

Background: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). Methods: We retrospectively reviewed 214 selected MM patients who were treated with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP. We performed univariate and multivariable analyses to assess the association between therapy outcomes and a series of clinical and biological features. Results: We identified 27 (10%) oligoprogressed patients treated locally with surgery (14), radiosurgery (11), and electrochemotherapy (2). TBP included PD-1 inhibitors (13) and BRAF/MEK inhibitors (14). The median progression-free survival post oligoprogression (PFSPO) was 14 months (5–19 95% confidence interval (C.I.)). In the univariate analysis, a significantly longer PFSPO was associated with complete response (CR), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, neutrophils/lymphocytes ratio (N/L) <2, and progression-free survival (PFS) at oligoprogression >11 months. Nevertheless, in the multivariable analysis, only CR and N/L <2 were found to be associated with longer PFSPO. Conclusions: In selected patients, local treatments contribute to controlling oligoprogression for a long time, allowing the continuation of systemic treatment and prolongation of overall survival (OS). Increasing biological and clinical knowledge is improving the accuracy in identifying patients to apply for local ablative therapies.

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Treatment Patterns and Outcomes Among Elderly Glioblastoma Patients at KFMC, Riyadh.

10.21203/rs.3.rs-619817/v1 ◽

2021 ◽

Author(s):

Amal Maire ◽

Ahmed M. Maklad ◽

Abdullah Altwairqi ◽

Wafaa AlShakweer ◽

Mohamed Senosi ◽

...

Keyword(s):

Adjuvant Treatment ◽

Performance Status ◽

Treatment Options ◽

Univariate Analysis ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Treatment Patterns ◽

Subtotal Resection ◽

Ecog Performance Status ◽

Significant Factors

Abstract IntroductionManagement of elderly patients with cancer is a controversial scenario and needs careful assessment and selection for aggressive radical treatment and chemotherapy protocols versus short-course radiotherapy without chemotherapy. Of note, definitions of the elderly vary in the glioblastoma (GBM) literature, with most of the randomized trials including patients aged 60, 65, or 70 years or older.Aim of the workTo evaluate treatment patterns and outcome among elderly GBM patients treated in KFMC, Riyadh. The primary endpoint is overall survival (OS) and the Secondary endpoint is progression-free survival (PFS) in relation to different treatment options and prognostic factors. MethodsThis is a retrospective study, included elderly GBM patients treated at KFMC, Riyadh, KSA between 1/2008 till 1/2018. 59 patients diagnosed with GBM ≥ 60 years were reviewed regarding radiotherapy (Rth) fractionation modalities, surgery, and chemotherapy (CTR) given in correlation to PFS, OS.Results59 patients were recruited in our study with median age 66 range (60-81) years, 47 (80%) were males. 37 patients (62.7%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, and 22 patients (37.3%) had PS < 2. Gross total resection (GTR) and subtotal resection (STR) was done in 49 (82.9%) patients, and the median follow-up was 12 months.38 (64%) patients received conventional Rth 60 Gray (Gy)/30 fractions or equal doses and 21 (36%) patients received hypofractionation Rth (40 Gy/15, 25 Gy/5 or 30 Gy/10 fractions).The median OS was 12 months (95% CI,9.52-14.48). For univariate analysis, receiving a conventional Rth and completion of 6 months adjuvant CTR were significant factors for O.S (P= 0.043 and 0.026) respectively. For multivariate those were also significant (P=0.035 and 0.002) respectively.The median PFS was 9 months (95% CI, 6.13-11.87). For univariate analysis PS, time to start adjuvant treatment, and completion of 6 months CTR were significant factors for PFS. For multivariate analysis starting adjuvant treatment within 2 months and completed CTR 6 months were significant factors (P=0.032 and 0.04) respectively. ConclusionElderly GBM patients who received conventional Rth and completed adjuvant 6 months CTR achieved a better OS, while starting adjuvant treatment earlier than 2 months and completed adjuvant CTR 6 months were associated with a better PFS, further prospective studies are needed to confirm our finding.

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Efficacy of anlotinib in advanced soft tissue sarcoma by age, gender, and ECOG performance status.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e23562 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e23562-e23562

Author(s):

Zhiwei Fang ◽

Yang Yao ◽

Jianqiang Cai ◽

Yihebali Chi ◽

Shusen Wang ◽

...

Keyword(s):

Performance Status ◽

Single Agent ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Ecog Performance Status ◽

Free Survival ◽

Cautious Interpretation ◽

Ecog Ps ◽

The Relationship ◽

Clinical Trial Information

e23562 Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. We evaluated the relationship between age, gender and ECOG performance status. Methods: Median PFS was analyzed in subgroups of age (≤40 y; > 40 y), gender (male; female) and ECOG performance status score (0; 1). All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. 79 patients (50.0%) were > 40 y. Median PFS was longer in patients of age > 40 y than ≤40 y (7.43 vs 5.43 months, P = 0.40). In patients receiving anlotinib, 76 patients (48.1%) were female and median PFS was longer in female than male (9.80 vs 4.43 months, P = 0.002). All enrolled patients had a Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 107 patients (67.7%) were with poor PS (ECOG PS = 1). The median PFS was longer in PS of 1(8.43 vs 4.73, P = 0.53) than PS of 0. Conclusions: In patients receiving anlotinib, longer mPFS was observed in patients of age > 40 y, ECOG PS = 1 and female. Clinical trial information: NCT02449343 .

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Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy

Biomolecules ◽

10.3390/biom11081099 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1099

Author(s):

Fadi Khreish ◽

Mona Wiessner ◽

Florian Rosar ◽

Zaidoon Ghazal ◽

Amir Sabet ◽

...

Keyword(s):

Molecular Imaging ◽

Performance Status ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Response Assessment ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Free Survival ◽

Pet Ct

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4–6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9–10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.

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Phase III Trial of Carboplatin and Paclitaxel With or Without Sorafenib in Metastatic Melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2012.42.1529 ◽

2013 ◽

Vol 31 (3) ◽

pp. 373-379 ◽

Cited By ~ 140

Author(s):

Keith T. Flaherty ◽

Sandra J. Lee ◽

Fengmin Zhao ◽

Lynn M. Schuchter ◽

Lawrence Flaherty ◽

...

Keyword(s):

Metastatic Melanoma ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Phase Iii ◽

Rank Test ◽

End Points ◽

Free Survival ◽

Log Rank Test ◽

The Difference

Purpose The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma. Patients and Methods In this double-blind, randomized, placebo-controlled phase III study, all patients received carboplatin at area under the [concentration-time] curve 6 and paclitaxel 225 mg/m2 intravenously once every 21 days with random assignment to sorafenib 400 mg orally twice per day on days 2 through 19 every 21 days or placebo. The primary end point was OS, and secondary end points included progression-free survival, objective tumor response, and toxicity. Results In all, 823 patients were enrolled over 34 months. At final analysis, the median OS was 11.3 months (95% CI, 9.8 to 12.2 months) for CP and 11.1 months (95% CI, 10.3 to 12.3 months) for CPS; the difference in the OS distribution was not statistically significant by the stratified log-rank test, stratified on American Joint Committee on Cancer (AJCC) stage, Eastern Cooperative Oncology Group (ECOG) performance status, and prior therapy (P = .878). Median progression-free survival was 4.9 months for CPS and 4.2 months for CP (P = .092, stratified log-rank test). Response rate was 20% for CPS and 18% for CP (P = .427). More patients on the CPS arm had grade 3 or higher toxicities (84% v 78%; P = .027), with increased rash, hand-foot syndrome, and thrombocytopenia accounting for most of the difference. Conclusion Sorafenib does not improve OS when given in combination with CP for chemotherapy-naive patients with metastatic melanoma. This study establishes benchmark end points for the CP regimen in first-line therapy of metastatic melanoma.

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Long-Term Tolerability and Efficacy of Carboplatin/Pemetrexed as Maintenance Therapy for a Patient With Lung Adenocarcinoma

10.21203/rs.3.rs-498643/v1 ◽

2021 ◽

Author(s):

Lixia Ju ◽

Juan Yang

Keyword(s):

Maintenance Therapy ◽

Lung Adenocarcinoma ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Ecog Performance Status ◽

Free Survival ◽

Term Tolerability ◽

First Time

Abstract BackgroundIt is widely known that platinum-based doublet chemotherapy (PBC) only can be applied to first-line patients with non-small cell lung cancer (NSCLC) with good performance for 4-6 cycles. However, in this case report the patient has been treated with PBC for 30 cycles and more than three years. Case presentationA 63-year-old Chinese man was diagnosed with stage IVa lung adenocarcinoma, with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0. This patient did not respond to pemetrexed alone, but respond to pemetrexed and carboplatin, and once the chemotherapy was interrupted for more than two months, the disease would progressed. Moreover, there was little adverse reactions (AE), so we have treated him with PBC for 30 cycles and the progression-free survival (PFS) will be more than three years.ConclusionsThis is the first time to report PBC as maintenance therapy in patients with NSCLC. We hope that oncologists will notice that some diseases are very aggressive, and maintenance therapy are very important to some patients and may help to get longer overall survival time.

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1185. Impact of Bloodstream Infections Caused by Multidrug-resistant Organisms on Performance Status: A KARS-Net Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1018 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S358-S358

Author(s):

Kyungmin Huh ◽

Doo Ryeon Chung ◽

Jae-Hoon Ko ◽

Young Eun Ha ◽

Si-Ho Kim ◽

...

Keyword(s):

Performance Status ◽

Univariate Analysis ◽

Eastern Cooperative Oncology Group ◽

Multivariable Analysis ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Ecog Performance Status ◽

E Coli ◽

Nationwide Surveillance ◽

The Impact

Abstract Background Infections caused by multidrug-resistant (MDR) organisms are associated with poorer clinical outcomes and higher economic burden. However, there has been limited data on the impact of MDR infection on the performance status of patients. Methods Patients with bloodstream infections by S. aureus, E. faecium, E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii have been identified prospectively as a part of a multicenter nationwide surveillance for antimicrobial resistance. Medical records of the patients enrolled from July 2015 through December 2016 were reviewed for demographic, clinical, microbiologic characteristics, and patient outcome. MDR was defined as MRSA, VRE, and nonsusceptibility to one or more agents in three or more different classes of antibiotics for Gram-negative bacteria. Performance status was evaluated by Eastern Cooperative Oncology Group (ECOG) Performance Status before admission and at discharge. Primary outcome was any decline in ECOG at discharge. Multiple logistic regression was used to identify independent risk factors for ECOG decline. Results A total of 19 hospitals participated to the network. The numbers of subjects were 410 for S. aureus, 392 for E. faecium, 708 for E. coli and K. pneumoniae, and 678 for P. aeruginosa and A. baumannii. In univariate analysis, bacteremia by MDR organisms was associated with ECOG decline only in patients with P. aeruginosa (18.4% vs. 10.3%, OR 1.962, 95% CI 1.132–3.399) and A. baumannii (27.6% vs. 11.8%, OR 2.834, 95% CI 1.328–6.045) infections. Patients with MDR K. pneumoniae infection had lower risk of ECOG decline (6.6% vs. 15.8%, OR 0.378, 95% CI 0.183–0.780). Multivariable analysis also showed that infection by MDR organism was independently associated with ECOG decline in patients with P. aeruginosa or A. baumannii infections (OR 2.068, 95% CI 1.478–2.895), but not with other MDR organisms. Comorbidities and initial ECOG showed higher effect size in patients with S. aureus and E. faecium infections. Conclusion In this large multicenter nationwide study, bloodstream infections caused by MDR P. aeruginosa and A. baumannii were associated with higher risk of decline in performance status at discharge. MDR status did not show association in infections by other species. Disclosures All authors: No reported disclosures.

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Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

10.21203/rs.3.rs-56332/v2 ◽

2020 ◽

Author(s):

Yuki Mukai ◽

Yuichiro Hayashi ◽

Izumi Koike ◽

Toshiyuki Koizumi ◽

Madoka Sugiura ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Clinical Stage ◽

Performance Status ◽

Univariate Analysis ◽

Stage Iv ◽

Progression Free Survival ◽

Late Toxicity ◽

Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

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Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.658331 ◽

2021 ◽

Vol 11 ◽

Author(s):

Juan Briones ◽

Maira Khan ◽

Amanjot K. Sidhu ◽

Liying Zhang ◽

Martin Smoragiewicz ◽

...

Keyword(s):

Prostate Cancer ◽

Predictive Factors ◽

Real World ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Markers ◽

Age At Diagnosis ◽

Free Survival ◽

Significant Difference

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

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The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.415 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 415-415

Author(s):

Husam Alqaisi ◽

Zachary William Neil Veitch ◽

Carlos Stecca ◽

Jeenan Kaiser ◽

Scott A. North ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Performance Status ◽

Progression Free Survival ◽

Response To Treatment ◽

Prognostic Impact ◽

First Line ◽

Ecog Performance Status ◽

Cancer Centre ◽

Platinum Based Chemotherapy ◽

Line Setting

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p<0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

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Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre

Clinical Sarcoma Research ◽

10.1186/s13569-019-0123-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Florence Chamberlain ◽

Sheima Farag ◽

Constance Williams-Sharkey ◽

Cecilia Collingwood ◽

Lucia Chen ◽

...

Keyword(s):

Kinase Inhibitor ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Individual Risk ◽

Duration Of Treatment ◽

Ecog Performance Status ◽

Third Line ◽

Grade 3 ◽

Dose Reductions

Abstract Background Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Methods Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Results Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. Conclusion Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

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