Salvage chemotherapy in the treatment of metastatic melanoma after progression on immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22019-e22019
Author(s):  
Payal Shah ◽  
Patrick Boland ◽  
Anna C. Pavlick
Keyword(s):  
Clinical Trial ◽  
Metastatic Melanoma ◽  
Retrospective Analysis ◽  
Checkpoint Inhibitors ◽  
Small Sample Size ◽  
Single Agent ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
Small Sample ◽  
Clinical Trial Evidence

e22019 Background: Immune-checkpoint inhibitors (ICI) have dramatically altered the prognosis of metastatic melanoma (MM); however, fifty percent of patients will not respond to ICI. For these patients, the next choice of treatment includes targeted therapy or a clinical trial if eligible. If these treatment choices have already been utilized or are not available to the patient, there may be value in attempting a course of salvage chemotherapy (CTX). Limited clinical trial evidence has demonstrated unexpected efficacy of CTX after prior progression on ipilimumab, offering higher disease control rates than expected from what is seen in first-line chemotherapy. The phenomenon of a “priming” effect of ICI on CTX efficacy has been shown in patients of various solid tumors after progression on anti-PD1/PD-L1 therapy. The purpose of this retrospective analysis is to evaluate the efficacy of salvage CTX after prior ICI therapy for patients with MM. Patients with ocular melanoma were excluded, as this tumor subtype is known to have reduced response to immunotherapy. Methods: By retrospective analysis, patients were included under an IRB approved waiver of consent. We identified patients with MM treated with ICI therapy between Jan, 2011 and July, 2019 who were subsequently treated with salvage CTX as a result of progression of disease (POD). Salvage CTX included dacarbazine, carboplatin, temozolomide, paclitaxel, or a combination. We assessed response rate, duration of response, and time to progression (TTP) from the onset of salvage CTX. Results: A total of 22 patients who satisfied the above criteria were identified. The majority of this population had a course of single agent ICI as well as a course of combination ICI prior to salvage CTX (72.7%, n = 16/22). 13 (59.1%) patients had POD on salvage CTX with a median TTP of 10.9 weeks. 9 (40.9%) patients responded to salvage CTX. 3 (13.6%) patients achieved a complete response, 4 (18.2%) patients achieved a partial response and 2 (9.1%) patients achieved stable disease. Mean durability of response was 53.6 weeks, ranging from 7-194 weeks. Conclusions: ICI “priming” prior to salvage CTX efficacy may improve disease responsiveness to CTX. This sequence of therapy may offer patients another reasonable treatment option. Despite the small sample size of this study, a prospective clinical trial in MM exploring CTX following ICI progression should be considered.

Incidence of Late-Relapse Germ Cell Tumor and Outcome to Salvage Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 6999-7004 ◽  
Author(s):  
Ellen A. Ronnen ◽  
G. Varuni Kondagunta ◽  
Jennifer Bacik ◽  
Stephanie Marion ◽  
Dean F. Bajorin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Germ Cell ◽  
Retrospective Analysis ◽  
Germ Cell Tumor ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
Cell Tumor ◽  
Late Relapse ◽  
First Line ◽  
Line Chemotherapy

Purpose To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. Patients and Methods Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. Results Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. Conclusion Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.

Neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant non-small cell lung cancer (NSCLC) and central nervous system (CNS) involvement: Findings from the SUMMIT basket trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9068-9068
Author(s):  
Jonathan Wade Goldman ◽  
Santiago Viteri Ramirez ◽  
Amit Mahipal ◽  
Jennifer Marie Marie Suga ◽  
Lisa DeFazio Eli ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Small Sample Size ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Small Sample ◽  
Cns Involvement ◽  
Cns Metastases ◽  
Cns Metastasis ◽  
Basket Trial

9068 Background: The phase 2 SUMMIT basket trial (NCT01953926) demonstrated efficacy of neratinib in patients with EGFR exon 18-mutant NSCLC [Boni et al. WCLC 2020]. Neratinib also has documented activity in HER2+ metastatic breast cancer with CNS metastases [Saura et al. SABCS 2020 & J Clin Oncol 2020]. Here we report neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant NSCLC and CNS involvement from SUMMIT. Methods: Patients with EGFR exon 18-mutant NSCLC were treated with single-agent neratinib (240 mg po daily). Prior EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and checkpoint inhibitors (IO) were allowed. Patients with stable, asymptomatic CNS metastasis were enrolled. Study endpoints: objective response rate (ORR) at week 8 (±1 week); ORR (RECIST 1.1 confirmed); duration of response (DOR); clinical benefit rate (CBR); progression-free survival (PFS); safety; biomarkers. Results: Baseline characteristics of 11 patients with EGFR exon 18-mutant NSCLC: median age 67 (range 56–83) years; ECOG PS 0/1 (45%/55%). Prior lines of therapies: 2 (range 1–3): EGFR TKIs (91%); chemotherapy (55%); IO (27%). 3/11 patients had baseline CNS metastasis and received radiation 8–22 months prior to study enrollment. Best CNS response in these 3 patients was stable disease with overall individual PFS of 1.9 (censored), 6.9 and 9.1 months and OS of 2.6 (censored), 17.7 (censored), and 17.9 months. Efficacy is summarized in Table. Efficacy summary: TKI-pretreated EGFR exon 18-mutant NSCLC cohort receiving neratinib monotherapy. Conclusions: Activity of single-agent neratinib was observed in prior TKI-exposed patients with EGFR exon 18-mutant NSCLC. Despite the small sample size of only 3 patients with baseline CNS metastases, findings suggest a potential role for neratinib as a systemic treatment option for patients with NSCLC and difficult-to-treat uncommon mutations with CNS involvement. The SUMMIT trial continues to enroll patients with EGFR exon 18-mutant NSCLC. Clinical trial information: NCT01953926. [Table: see text]

Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma.

1987 ◽  
Vol 5 (7) ◽  
pp. 1078-1082 ◽  
Author(s):  
R F Morton ◽  
E T Creagan ◽  
S A Cullinan ◽  
J A Mailliard ◽  
L Ebbert ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Soft Tissue ◽  
Phase Ii ◽  
Small Sample Size ◽  
Single Agent ◽  
Complete Response ◽  
Small Sample ◽  
Combination Regimen ◽  
Phase Ii Trials ◽  
Phase Ii Studies

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.

Bendamustine Demonstrates Promising Activity in Post-Brentuximab Failure Hodgkin Lymphoma Patients Who Had Also Failed a Prior Autologous HCT and Facilitates Successful Bridging to Allogeneic HCT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5359-5359
Author(s):  
Jean Elcheikh ◽  
Radwan Massoud ◽  
Elie Fares ◽  
Mohamed A Kharfan-Dabaja ◽  
Jisr Tamima ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Checkpoint Inhibitors ◽  
Small Sample Size ◽  
Medical Center ◽  
Single Agent ◽  
Objective Response ◽  
Small Sample ◽  
Study Endpoint ◽  
Primary Study

Abstract BACKGROUND: Hodgkin's lymphoma (HL), although considered a curable neoplasm in adults, could be associated with a very poor prognosis when refractory to primary induction therapy or when it relapses within 12 months from an autologous stem cells transplant (auto-HCT).The optimal treatment of patients with heavily pretreated/refractory HL is controversial. Brentuximabvedotin(Bv) is an active single agent in this context; unfortunately, there are nowell establishedtherapies when patients fail to respond or progress afterBv. Encouraging results were recently described with checkpoint inhibitors. Similarly, data pertaining to efficacy ofbendamustine(Benda) shows encouraging activity in various refractory lymphomas. PATIENTS AND METHODS: We included in this study adult patients with HL who relapsed post auto-HCT and were refractory to or progressed after salvageBvand were treated withBenda as salvage therapy with an intention to proceed with anallo-HCT. This study was conducted in two major centersin Lebanon,the American university of Beirut Medical Center (AUBMC) andMakasseduniversity hospital. We identified 12 eligible cases.The primary study endpoint was objective response rate (ORR). The secondary endpoint evaluated successful rate of bridging into anallo-HCT. RESULTS: The median follow-up times from Auto-HCT and from Benda salvage were 35 (14-59) and 10 (4-35) months, respectively. The median age of patients was 27 years (17-54).All patients hadBvas salvage therapy post Auto-HCT, and all of them progressed after a median of 4 (3-6) cycles.Clinical characteristics are outlined in Table 1. Patients received a median of 6 cycles (2-8) of Benda.The treatment was well tolerated, with rather infrequent adverse events and transient and manageable toxicities. The ORR was 75%, in 9 of 12 patients, with 43% obtaining a complete response. Eventually, 6 of 9 proceeded toallo-HCT using a matched related donor, and the remaining 3 patients are planned forallo-HCT. Only one patient died from disease progression after 24 months postallo-HCT. Two of 3 patients who progressed followingbendareceived salvage therapy withnivolumaband are being planned forhaplo-identical transplant while the third one is being planned for therapy withnivolumab. From the initiation ofbenda, the median duration of response for the 9 patients was 10 months (4-29); all these patients had maintained a continuous response at the last follow-up examination. CONCLUSION: Notwithstanding the limitations associated with our analysis, namely a small sample size and its retrospective nature, these results suggest a role forbendamustinein postBvfailures.These findings also provide the basis to evaluate the concept of Benda as a bridge toallo-HCT in a large prospective study. Disclosures Kharfan-Dabaja: Incyte: Speakers Bureau; Seattle Genetics: Speakers Bureau.

Analysis of metastatic melanoma treated with immune checkpoint inhibitors and the rates of adverse events of colitis and hepatitis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21591-e21591
Author(s):  
Emily Horan ◽  
Melissa Arneil ◽  
Wen Xu ◽  
Victoria Atkinson
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Complete Response ◽  
Treatment Regimens ◽  
Organ Systems ◽  
Oral Steroids ◽  
Intravenous Steroids

e21591 Background: Immune checkpoint inhibitors (CPI) are widely used in metastatic melanoma (MM), where it has markedly improved survival outcomes. ICI induced autoimmune adverse reactions (irAE) manifest in all organ systems and are due to over-activation of the immune system. Clinically relevant irAE are colitis and hepatitis as drivers of morbidity and mortality. Methods: Data was collected from a single centre (Princess Alexandra Hospital) from the electronic medical records system and immunotherapy prescribing software. Patient demographics, treatments, complications and outcomes were recorded from 2016-2019. Eligible patients had to have received immunotherapy (pembrolizumab, ipilimumab, or nivolumab) and experienced colitis or hepatitis toxicity. Trial patients were excluded. Results: The cohort of 337 patients who had received immune therapy, 18% (n = 61) had hepatitis or colitis, mean age was 56 years, 64% male. The majority were stage 4d 28% (n = 17). Braf wildtype accounted for 56% (n = 34). The highest rates of irAE occurred on combination ipilimumab and nivolumab 56% (n = 34), 10% nivolumab (n = 6), 3% (n = 2) ipilimumab, and 31% (n = 19) pembrolizumab monotherapy. Colitis affected 61% of patients (n = 37), 30% (n = 18) were grade 3 severity. Hepatitis affected 48% (n = 29), 18% (n = 32) were grade 1. The majority required oral steroids (80%, n = 49), followed by intravenous steroids (51%, n = 31), infliximab (18%, n = 11) and mycophenolate in 5% (n = 3). Hospitalisation occurred in 56% (n = 34), 20% (n = 12) requiring treatment cessation. Progressive disease occurred in 62% (n = 38), and 13% (n = 8) had a complete response. Conclusions: The findings of this analysis mirror current literature with immunotherapies used, rates and severity of irAE. The management of irAE also aligned with current guidelines. Further research is required to investigate patient factors increasing the risk of developing irAE, and ideal treatment regimens. Analysing this large cohort, the incidence of toxicity was 17%, predominantly colitis followed by hepatitis. Patients were severely impacted requiring significant interventions to manage toxicity, hospitalisation and morbidity.

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient

2019 ◽  
Vol 26 (2) ◽  
pp. 496-499 ◽  
Author(s):  
Saadettin Kilickap ◽  
Deniz C Guven ◽  
Oktay H Aktepe ◽  
Burak Y Aktas ◽  
Omer Dizdar
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Complete Response ◽  
Duration Of Treatment ◽  
Treatment Protocols ◽  
Real Life Data ◽  
Heavily Pretreated ◽  
Drug Free

In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

scholarly journals Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Caitlyn N. Myrdal ◽  
Srinath Sundararajan
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Optimal Sequencing ◽  
The Right

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance is frequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term response but displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limited data regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentleman with advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantial response to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial of combination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses can be elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.

Randomized phase II study of the safety and efficacy of a human anti-αv integrin monoclonal antibody (CNTO 95) alone and in combination with dacarbazine in patients with stage IV metastatic melanoma: 12-month results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9029-9029
Author(s):  
C. Loquai ◽  
A. Pavlick ◽  
D. Lawson ◽  
R. Gutzmer ◽  
J. Richards ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Research And Development ◽  
Metastatic Melanoma ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Safety And Efficacy ◽  
To Receive

9029 Objectives: Evaluate the safety and efficacy of CNTO 95, a human anti-αv integrin monoclonal antibody, when administered alone or in combination with dacarbazine (DTIC). Methods: Patients with Stage IV metastatic melanoma were randomized 1:1:1:1 to receive 5 or 10mg/kg CNTO 95 alone, or DTIC (1000mg/m2) + either 10mg/kg CNTO 95 or placebo administered intravenously once every 3 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. DTIC arms were blinded; single-agent arms were open-label. The primary endpoint was progression free survival (PFS); secondary endpoints included partial response (PR), complete response (CR), stable disease (SD) and overall survival (OS). Major safety endpoints included the incidence of adverse events (AEs) and serious AEs (SAEs). Results: Patients were randomized to receive 5mg/kg CNTO 95 (n=32), 10mg/kg CNTO 95 (n=33), CNTO 95+DTIC (n=32), or placebo+DTIC (n=32). Baseline demographics were similar across groups. The median PFS for CNTO 95+DTIC was 75 days, placebo+DTIC was 54 days and both CNTO 95 alone arms were 42 days. Six patients achieved PR (2–10mg/kg CNTO 95, 1-CNTO 95+DTIC, 3-placebo+DTIC); one patient achieved CR (CNTO 95+DTIC). A higher proportion (43.3%) of patients achieved SD ≥ 12 wks in the CNTO 95+DTIC group compared with the other 3 groups (<20.0%). The median survival was 11.0 months for the patients in the CNTO 95+DTIC arm, 9.8 months and 14.9 months for the 5mg/kg and 10mg/kg arms, and 8.0 months for those in the DTIC control arm. The most common AEs were headache, nausea, fatigue, pyrexia, vomiting and transient uveitic reactions. Three patients (1–5mg/kg, 2-CNTO 95+DTIC) discontinued treatment due to AEs. A higher proportion of patients experienced SAEs in the placebo+DTIC group (29.0%) than in the 5mg/kg (12.9%), 10mg/kg (16.2%) or CNTO 95+DTIC (18.8%) groups. Conclusions: CNTO 95 alone or combined with DTIC was generally well tolerated. In patients with Stage IV metastatic melanoma, a trend toward improvement in PFS, OS and disease control was demonstrated with CNTO 95+DTIC. Centocor, Centocor Research and Development, Inc. Centocor Research and Development, Inc. Johnson & Johnson Centocor Research and Development, Inc. No significant financial relationships to disclose.

A phase II clinical trial of ganetespib (STA-9090) in previously treated patients with advanced esophagogastric cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4090-4090 ◽  
Author(s):  
Eunice Lee Kwak ◽  
Lipika Goyal ◽  
Thomas Adam Abrams ◽  
Amanda Carpenter ◽  
Brian M. Wolpin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Progression ◽  
Single Agent ◽  
Heat Shock Protein 90 ◽  
Complete Response ◽  
Median Number ◽  
Oncogenic Signaling ◽  
Her2 Positive ◽  
Phase 2 Trial ◽  
Ecog Ps

4090 Background: Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2 or MET, or mutations in PIK3CA, EGFR, or BRAF. These genes encode clients of the molecular chaperone heat-shock protein 90 (HSP90), and inhibition of HSP90 may promote the degradation of these oncogenic signaling proteins. Ganetespib is a novel triazolone heterocyclic inhibitor of HSP90 that is a biologically rational treatment strategy for advanced EG cancers. Methods: This was a multicenter, single-arm Phase 2 trial. Eligibility: Histologically confirmed advanced EG cancer; progression on ≤ 2 lines of systemic therapy; ECOG PS 0-1. Treatment: Ganetespib 200mg/m2IV on Days 1, 8, and 15 of a 28-day cycle. Primary endpoint: overall response rate (ORR). Results: 26/28 patients enrolled received ≥ 1 dose of drug. The characteristics of the 26 patients were: male 77%, median age 64 years old; ECOG PS 0/1 42/58%; median number of prior therapies 2; esophageal/GEJ/gastric 27/42/31%; prior platinum 92%, prior fluoropyrimidine 88%, prior taxane 38%, prior trastuzumab 15%. Median follow-up was 83 days. The most common drug-related adverse events were: diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common Grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). 14/26 required ≥ 1 dose modification. 22/26 patients completed at least 2 cycles of ganetespib and were evaluable for response. One complete response was seen, and this patient continues on treatment as of cycle 31 (27.5 mos). Molecular characterization of this patient’s tumor revealed a KRAS mutation in codon 12. The ORR was 1/26 (4%). Two of six patients with HER2-positive disease achieved 12% and 19% tumor reduction from baseline, respectively. TTP was 48 days (1.6 mos) and OS was 83 days (2.8 mos). Conclusions: Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug. The molecular determinants of response, however, have yet to be fully characterized. Clinical trial information: CT01167114.

Retrospective analysis of sorafenib as first or second target therapy in mRCC patients in Italian centers: An update.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15524-e15524
Author(s):  
Lisa Derosa ◽  
Angela Gernone ◽  
Franco Morelli ◽  
Teodoro Sava ◽  
Fable Zustovich ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Retrospective Analysis ◽  
Target Therapy ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Daily Clinical Practice ◽  
Duration Of Treatment ◽  
Ecog Performance Status

e15524 Background: With several agents available for the treatment of metastatic renal cell carcinoma (mRCC) a better understanding of their use in daily clinical practice is fundamental in the decision-making process. Methods: The REtrospective analysis of Sorafenib (So) as 1st or 2nd targET therapy (RESET) in mRCC was a retrospective, observational field study that assessed the use and safety of So in clinical practice in Italian centers. Treatments were determined by physicians per local prescribing guidelines. Patients (pts) treated with So single agent as 1st or 2nd target therapy (TT) for mRCC between 1st Jan 2008 and 31st Dec 2010 were eligible for inclusion. Endpoints included safety, overall survival (OS), progression-free survival, response rate and treatment duration. Subgroup analyses included age, ECOG performance status, prior therapy, number of metastases and line of TT with So. Results: From Feb to Jul 2012, 358 pts from 37 Italian centers were enrolled. The most common ≥ grade 3 drug-related adverse events were hand-foot skin reaction (6.7%), rash (2.2%), hypertension, fatigue and diarrhea (1.7% each). In the overall population, median OS was 17.2 months (mos) (95% CI 15.4 – 19.6 mos) and median PFS was 5.9 mos (95% CI 4.9-6.7 mos). Median duration of treatment with So was 5.03 mos. Disease control (complete response + partial response + stable disease) was observed in 198(56%) pts. In pts receiving So as first or as second TT median OS was 19.9 mos (95% CI 15.9-25.3 mos) and 16.3 mos (95% CI 13.0-18.2 mos) respectively. In the subgroup of pts treated with So 1st TT followed by sunitinib (Su) 2nd TT (44 pts) and Su 1st TT followed by So 2nd TT (173 pts), median OS was 30.4 mos (95% CI 22.0-34.8 mos) and 16.6 mos (95% CI 13.1-18.2 mos) respectively. There were 269(76%) pts that received a total of 2 lines of therapy for mRCC, 133(38%) pts 3 lines and 43(12%) pts 4 lines of therapy. Conclusions: The efficacy and safety profile of So in the setting of Italian community-based daily clinical practice was similar to data reported in prospective clinical trials. The efficacy of So was observed in both the subgroups of pts receiving So as either the first or second TT for mRCC, with intriguing OS data in first line.

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