Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9006-9006
Author(s):  
Joshua Bauml ◽  
Byoung Chul Cho ◽  
Keunchil Park ◽  
Ki Hyeong Lee ◽  
EUN KYUNG CHO ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Combination Regimen ◽  
Resistance Mutations ◽  
Tumor Biopsy ◽  
Potential Biomarker ◽  
Treatment Naïve ◽  
Exon 19 Deletion ◽  
Potential Biomarkers

9006 Background: Preliminary efficacy was observed with the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a 3rd-generation tyrosine kinase inhibitor, in both treatment-naïve and osimertinib (osi)-relapsed patients (pts) with EGFRm NSCLC (Cho Ann Oncol 2020;31:S813). We present updated results of the combination in osi-relapsed pts, including an analysis of potential biomarkers of response. Methods: Pts with EGFR exon 19 deletion or L858R mutation NSCLC, who had progressed on osi without intervening chemotherapy, were enrolled in the combination cohort of the ongoing CHRYSALIS study (NCT02609776). With pre-treatment tumor biopsies and ctDNA collected prospectively, pts received the combination dose of 1050/1400 mg amivantamab + 240 mg lazertinib to assess safety and efficacy in the osi-relapsed population. Response was assessed by investigator per RECIST v1.1. Osi-resistance mutations or amplifications in EGFR/MET identified by next-generation sequencing (NGS) in either ctDNA or tumor biopsy (biomarker-positive [pos]), were evaluated for enriching response. Immunohistochemistry (IHC) staining for EGFR and MET expression was also explored as a potential biomarker for response. Results: Of the 45 osi-relapsed pts, 36% (95% CI, 22–51) had a confirmed response (1 complete response and 15 partial responses [PR]). At a median follow-up of 8.2 mo (1.0–11.8), 20/45 pts (44%) remain on treatment. With 11/16 pts (69%) continuing in response (2.6–9.6+ mo), median duration of response has not been reached (NR). The median progression-free survival (mPFS) was 4.9 mo (95% CI, 3.7–8.3). In total, 44/45 pts were evaluable by ctDNA and 29/45 by tumor NGS. Genetic testing identified 17 biomarker-pos pts, of whom 8 (47%) responded. Of the remaining 28 pts, 8 (29%) responded. Among these 28 pts, 18 had unknown mechanisms of osi-resistance (8 PR) and 10 had non-EGFR/MET mechanisms of resistance identified (none responded). The mPFS (95% CI) for biomarker-pos and remaining pts was 6.7 mo (3.4–NR) and 4.1 mo (1.4–9.5), respectively. Adequate tissue was available for 20 pts to perform IHC testing for EGFR and MET–9/10 (90%) IHC high (combined EGFR+MET H score>400) pts responded to treatment, while 1/10 IHC low pts responded to treatment. Conclusions: Treatment with the combination of amivantamab and lazertinib yielded responses in 36% of chemotherapy-naïve pts who progressed on osi. Among these pts, genetic EGFR and MET-based biomarkers of resistance identified a subgroup of pts more likely to respond to amivantamab and lazertinib, although additional pts lacking identified resistance markers also responded. An IHC-based approach may identify pts most likely to benefit from the combination regimen, but further investigation is warranted. Clinical trial information: NCT02609776.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAFV600E-mutant metastatic melanoma

2020 ◽  
Vol 26 (7) ◽  
pp. 1754-1758
Author(s):  
Mesut Yilmaz ◽  
Şermin Güven Meşe
Keyword(s):  
Metastatic Melanoma ◽  
Poor Prognosis ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Braf Inhibitors ◽  
Free Survival ◽  
Therapy Options ◽  
Modern Era ◽  
Braf Mutant

Introduction Patients with distant metastatic melanoma has a poor prognosis, with a reported median survival time of six to eight months. In modern era, survival has prolonged with the immunotherapy and targeted therapy options. Potent and selective BRAF inhibitors have been developed that specifically inhibit mutated BRAF over other RAF kinases. Vemurafenib was the first selective tyrosine kinase inhibitor developed to target the V600E allele of BRAF-mutant melanoma. Case Report In this report, we present a case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years. Management and Outcome The patient is still being treated with vemurafenib and radiologic complete response is ongoing for about seven years. Discussion Patients treated with BRAF inhibitors monotherapy had promising response rates and improvement in the progression-free survival and overall survival, but melanoma cells became resistant very quickly, affecting the progression. In this case, we present a case that has permanent response to vemurafenib monotherapy.

Exceptional responses in patients with upper gastrointestinal malignancies enrolled in first-in-man studies: 2002-2012.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 311-311
Author(s):  
Zachary L Reese ◽  
Danielle Tometich ◽  
Shiven B. Patel ◽  
Sunil Sharma ◽  
Ignacio Garrido-Laguna
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patient ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pancreatic Cancer Patient ◽  
Gastrointestinal Malignancies ◽  
Upper Gastrointestinal

311 Background: First-in-man (FIM) studies test the efficacy and safety of novel therapeutic agents with proven in vitro activity when used for the first time in humans. Patients with advanced upper gastrointestinal malignancies (UGIM) have limited systemic treatment options. We established a database of FIM studies published from 2002-2012 to identify exceptional responders in patients with UGIM. Methods: Using a Scopus search, we compiled a database of published FIM studies enrolling patients with UGIM between 2002 and 2012. We identified exceptional responders to therapy among these patients as a complete response or a partial response lasting at least 6 months. Results: We identified 84 FIM studies enrolling at least one patient with UGIM. In total 554 patients with UGIM were enrolled including 290 pancreatic adenocarcinomas (52.3%), 110 gastric adenocarcinomas (19.9%), 83 esophageal carcinomas (15.0%), 41 hepatocellular carcinomas (7.4%), and 30 cholangiocarcinomas/gallbladder carcinomas (5.4%). One patient with pancreatic cancer treated with bosutinib, a src kinase inhibitor, had a complete response with a progression-free survival (PFS) of 42 months. Four partial responses were reported including one pancreatic cancer patient treated with CHR-3996, a histone deacetylase inhibitor (PFS 12 mo); two pancreatic cancer patients treated with trametinib, a MEK inhibitor (10 and 11.75 mo); and one cholangiocarcinoma patient treated with SB-743921, a kinesin inhibitor (11 mo). Two additional partial responses were noted without available PFS data including one pancreatic cancer patient treated with KOS-1584, a second generation epothilone, and one gastric cancer patient treated with apatinib, a VEGFR-2 inhibitor. Conclusions: Exceptional responses are seen in patients with UGIM enrolled in FIM studies. Actionable genetic aberrations may be driving disease in these patients. Further studies are needed to understand these responses at the molecular level. These molecular studies could open new treatment opportunities for patients with advanced UGIM.

Efficacy of tyrosine kinase inhibitors (TKIs) based on the ALK resistance mutations on amplicon-based liquid biopsy in ALK positive non-small cell lung cancer (NSCLC) patients (pts).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3055-3055
Author(s):  
Laura Mezquita ◽  
Aurélie Swalduz ◽  
Cecile Jovelet ◽  
Sandra Ortiz-Cuaran ◽  
David Planchard ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Next Generation ◽  
Resistance Mutations ◽  
Durable Response ◽  
Free Survival ◽  
Alk Positive ◽  
Nsclc Patients

3055 Background: Acquired ALK resistance mutations (mut.) are the main mechanism of tyrosine kinase inhibitor (TKI) resistance (30-50%). While next-generation TKIs are more active on mut. than earlier TKIs, compound ALK resistance are associated with failure to next-generation TKIs. We evaluated the clinical utility of detecting ALK resistance mutations in blood to predict TKI efficacy. Methods: ALK positive advanced NSCLC pts were prospectively enrolled between Oct. 2015 and Aug. 2018 in 8 French institutions. Prospective samples were collected; ctDNA was analyzed by amplicon-based Inivata InVisionFirst-Lung. Results: A total of 101 pts with advanced ALK positive NSCLC were enrolled and 328 samples collected. In samples collected at TKI failure (N=74), we detected 9 single and 7 complex (≥2) ALK resistance mut. (22%), associated with EML4-ALK variant 3 (38%) vs. variant 2 (13%) vs. variant 1 (none); 30% had other somatic mut. (mainly TP53 and KRAS, PI3KCA, MET, etc.). No mutations were detected in 48% of samples (ctDNA neg). ALK mut. were more frequent after 2nd/3rd generation TKI (43% post-lorlatinib (7), 29% post-2nd gen. (31), 11% post-crizotinib (36)). ALKG1202R was the most common, as single (n=3) or complex mut. (n=4). The median overall survival (mOS) was 100.4 mo. (95% CI 41.9-158.9) and the median progression free-survival (mPFS) to subsequent line was 2.8 mo. (0.7-4.9). Patients with ctDNA neg had mOS of 105 mo. (39.3-172.1) vs. 58.5 mo. (33.1-84.0) if ≥1 ALK mut. vs. 44.1 mo. (20.0-68.2) if others ( P=0.001). Pts with the complex ALK mut. had worse OS compared to singles ALK mut. (mOS 26.9 mo. vs. 58.5 mo., P=0.001); ALK complex mut. were associated with poor efficacy to subsequent therapy (PFS <3 mo. in 57%; no cases with PFS >6 mo.) vs. single mut., with longer PFS (PFS >6 mo. in 56%). Detectable ALKG1202R mut. were associated with shorter median OS (58.3 mo.; 7.9-109.1) vs. overall population; 86% of cases developed rapid PD (PFS <3mo.) to subsequent therapy with only one durable response to lorlatinib (PFS >6mo.). Conclusions: The absence of ctDNA mutations at TKI failure was associated with prolonged OS, whereas complex ALK mutations at TKI failure may predict resistance to subsequent therapy. Larger and specifically designed studies should be performed to validate these findings.

scholarly journals Case Report: Favorable Response to the Tyrosine Kinase Inhibitor Apatinib in Recurrent Merkel Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiyi Feng ◽  
Xin Song ◽  
Renbing Jia
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lower Eyelid ◽  
Merkel Cell ◽  
The Right

BackgroundAs angiogenesis is an essential step in tumor growth and metastasis, the tyrosine kinase inhibitor (TKI) apatinib has become a revolutionary anticancer therapy across various malignancies. However, its efficiency and safety in Merkel cell carcinoma (MCC) are uncertain.Case presentationThe current study described the case of a 91-year-old man who presented with a 3.2 × 3.0 × 2.2 cm rapidly growing, solitary tumor of the right lower eyelid. It was diagnosed as MCC pathologically. Twenty-seven days after the surgery, the patient returned to the hospital with recurrent MCC. Apatinib was then administered to this patient. The patient had a complete response (CR) to apatinib after 4.4 months of targeted therapy. Twenty-seven months of progression-free survival (PFS) was achieved with controllable treatment-related adverse events (AEs).ConclusionTreatment with apatinib demonstrated clinical benefit in our patient with recurrent MCC, highlighting its potential utility in other MCC patients. Further clinical trials are needed to determine the efficacy and safety of apatinib in MCC patients.

scholarly journals Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-naïve study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jason K. Sicklick ◽  
Shumei Kato ◽  
Ryosuke Okamura ◽  
Hitendra Patel ◽  
Mina Nikanjam ◽  
...  
Keyword(s):  
Disease Control ◽  
Progression Free Survival ◽  
Complete Response ◽  
Disease Control Rate ◽  
Unknown Primary ◽  
Combination Therapies ◽  
First Line ◽  
Free Survival ◽  
Treatment Naïve ◽  
Matching Score

Abstract Background Malignancies are molecularly complex and become more resistant with each line of therapy. We hypothesized that offering matched, individualized combination therapies to patients with treatment-naïve, advanced cancers would be feasible and efficacious. Patients with newly diagnosed unresectable/metastatic, poor-prognosis cancers were enrolled in a cross-institutional prospective study. Methods A total of 145 patients were included in the study. Genomic profiling (tissue and/or circulating tumor DNA) was performed in all patients, and PD-L1 immunohistochemistry, tumor mutational burden, and microsatellite status assessment were performed in a subset of patients. We evaluated safety and outcomes: disease-control rate (stable disease for ≥ 6 months or partial or complete response), progression-free survival (PFS), and overall survival (OS). Results Seventy-six of 145 patients (52%) were treated, most commonly for non-colorectal gastrointestinal cancers, carcinomas of unknown primary, and hepatobiliary malignancies (53% women; median age, 63 years). The median number of deleterious genomic alterations per patient was 5 (range, 0–15). Fifty-four treated patients (71%) received ≥ 1 molecularly matched therapy, demonstrating the feasibility of administering molecularly matched therapy. The Matching Score, which reflects the percentage of targeted alterations, correlated linearly with progression-free survival (R2 = 0.92; P = 0.01), and high (≥ 60%) Matching Score was an independent predictor of improved disease control rate [OR 3.31 (95% CI 1.01–10.83), P = 0.048], PFS [HR 0.55 (0.28–1.07), P = 0.08], and OS [HR 0.42 (0.21–0.85), P = 0.02]. Serious adverse event rates were similar in the unmatched and matched groups. Conclusions Personalized combination therapies targeting a majority of a patient’s molecular alterations have antitumor activity as first-line treatment. These findings underscore the feasibility and importance of using tailored N-of-1 combination therapies early in the course of lethal malignancies. Trial registration I-PREDICT (NCT02534675) was registered on August 25, 2015.

scholarly journals Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response

2020 ◽  
Vol 52 (2) ◽  
pp. 594-603 ◽  
Author(s):  
Junho Kang ◽  
Jae Ho Jeong ◽  
Hee-Sang Hwang ◽  
Sang Soo Lee ◽  
Do Hyun Park ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Current Standard ◽  
Durable Response ◽  
Tract Cancer ◽  
Potential Biomarker

Purpose The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated. Materials and MethodsIn this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks. ResultsBetween May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049). Conclusion Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response observed in adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 41-41 ◽  
Author(s):  
D. Ilson ◽  
Y. Y. Janjigian ◽  
M. A. Shah ◽  
L. H. Tang ◽  
D. P. Kelsen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Node Disease ◽  
Grade 3

41 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial combining sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We are studying single agent sorafenib in a phase II trial with the primary endpoint to assess progression free survival (PFS). Secondary endpoints include response and therapy tolerance. Methods: Patients (pts) with measurable metastatic E and GEJ cancer with no more than 3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Sixteen of 35 pts have been accrued and 14 are currently evaluable. 13 male, 3 female, median KPS 80%, age 58, GEJ 7, E 9, squamous 2, adenocarcinoma (AC)14. An ongoing complete response (11+ months) was observed in a pt with biopsy proven metastatic neck lymphadenopathy (E primary AC, recurrence after prior chemoradiotherapy and surgery). A second pt (GEJ AC) had protracted stable disease in bulky celiac node disease (15+ months). Grade 3 toxicity was limited to skin rash (1 pt), hand foot reaction (1 pt), and fatigue (1 pt). Only 3 of 14 pts (21%) had early disease progression at 2 months or less. Median PFS 4 mos, 4 patients (29%) continue on therapy for more than 7 months. The majority of tumors tested positive for phospho-erk by immunohistochemistry (11/14, 79%). Conclusions: The observation of a durable complete response and protracted stable disease to sorafenib in E cancer is remarkable. Further accrual continues to define PFS. Supported by a grant from Bayer. [Table: see text]

Outcomes of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with pazopanib after progression on other targeted therapies (TT): Updated results.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 367-367
Author(s):  
Marc Ryan Matrana ◽  
Cihan Duran ◽  
Aditya Shetty ◽  
Lianchun Xiao ◽  
Bradley J. Atkinson ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Median Number ◽  
Cox Proportional Hazards ◽  
Clinical Activity ◽  
Pancreatic Metastases ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

367 Background: Pazopanib is an multi-tyrosine kinase inhibitor shown to prolong progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety on its use after TT are limited. Methods: We retrospectively reviewed records of consecutive pts with mRCC who were treated with pazopanib between November 2009-November 2011 after having progressive disease (PD) with other TT. Radiographic response was assessed by a blinded radiologist using RECIST v1.1 criteria. PFS and overall survival (OS) were estimated by the Kaplan-Meier method. Hazard ratios (HR) were estimated by fitting univariable and multivariable Cox proportional hazards models to evaluate the association of PFS with patient co-variates. Results: 112 pts (median age 63 years, 67% male, 83% clear cell) met inclusion criteria. Median number of previous TT was 2 (range 1-5). 85 events (PD or death) occurred. 14 pts (12.5%) had a partial response. Median PFS was 5.7 months (95% CI: 4.3-8.9 months). PFS was significantly associated with male gender (HR=0.55; 95% CI: 0.34-0.87; p=0.011), clear-cell histology (HR=0.42; 95% CI: 0.24-0.74; p=0.0031), number of metastatic sites (HR= 1.26; 95% CI: 1.05-1.52; p=0.0123), pancreatic metastases (HR=0.40; 95% CI: 0.18-0.85;p=0.0185), Karnofsky PS< 80 (HR=2.07; 95% CI: 1.22-3.48; p=0.0062), and elevated LDH (HR=1.63; 95% CI: 1.03-2.573; p=0.035). Median OS was 16.9 months (95% CI: 10.3–21.9). 26% of pts were still receiving pazopanib at the time of analysis. 51% discontinued pazopanib due to PD and 12% died of PD on treatment. 11% discontinued pazopanib due to adverse events (AEs). There were no treatment related deaths. Common AEs included fatigue (43%), increase LFTs (34%), diarrhea (28%), nausea/vomiting (14%), anorexia (14%), hypertension exacerbation (12%), and hypothyroidism (11%). 89% of AEs were grade 1/2. Conclusions: Pazopanib demonstrated meaningful clinical activity in heavily pretreated pts with mRCC following PD with other TT. AEs were mild/moderate and manageable.

Overall survival (OS) of sorafenib (So) plus interleukin-2 (IL-2) versus So alone in patients with treatment-naive metastatic renal cell carcinoma (mRCC): Final update of the ROSORC trial.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 356-356
Author(s):  
Giuseppe Procopio ◽  
Elena Verzoni ◽  
Sergio Bracarda ◽  
Sergio Ricci ◽  
Laura Ridolfi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Single Agent ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Rank Test ◽  
Combination Regimen ◽  
First Line ◽  
Open Label ◽  
Treatment Naïve

356 Background: A randomized phase II trial evaluating So plus IL-2 versus So alone as first-line treatment of mRCC, did not show any difference in progression-free survival (PFS) (primary endpoint) between the two groups. The final overall survival analysis is here reported. Methods: In this open-label phase II study, 128 patients with mRCC were randomized to receive either oral So 400 mg bid continuous dosing plus IL-2 4.5 MIU subcutaneously administered 5 times weekly for 6 weeks every 8 weeks (Arm A), or So alone (Arm B). At relapse, most patients of the two arms underwent treatment with other targeted therapies (TTs) including sunitinib, everolimus, and axitinib. Overall survival was estimated by Kaplan-Meier method and compared by two-sided log-rank test. Results: According to Motzer criteria 55 % of the patients were low risk in both arms, and 41% and 39% were intermediate risk in Arm A and B respectively. After a median follow-up time of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in Arm A and B, respectively (p = 0.667). Five-year OS was 26.3% (95% CI: 15.9-43.5) for the combination arm and 23.1% (95% CI: 13.2-40.5) for single agent arm. The overall number of death was 85, 42 of whom in the So monotherapy group. Median PFS survival was 7.3 and 6.9 months for Arm A and B, respectively (p = 0.109). Overall, 49 (77%) and 48 (75%) patients in Arm A and B, respectively, received at least one subsequent targeted therapy (TTs). The most common adverse events (AEs) in both arms were asthenia, hand-foot syndrome, hypertension and diarrhoea. Grade 3-4 AEs were documented in 38% of patients treated with the combination regimen and in 25% of those undergoing single agent treatment. Conclusions: The OS results suggest an improved outcome in patients with mRCC treated with TTs which appears independent of the treatment initially administered. This prospective study, regarding use of sorafenib in first line of treatment, was associated with a surprising median OS. Clinical trial information: NCT00609401.

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