Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and low Karnofsky performance status: Results from the CheckMate 920 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 315-315
Author(s):  
Thomas E. Hutson ◽  
Bradley Curtis Carthon ◽  
Jeffrey Yorio ◽  
Sunil Babu ◽  
Heidi Ann McKean ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Grade 3

315 Background: Combination therapy with nivolumab + ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability for patients (pts) with previously untreated advanced renal cell carcinoma (aRCC). Most pivotal clinical trials in pts with aRCC have excluded pts with low Karnofsky performance status (KPS; < 70%). CheckMate 920 is a multi-arm, phase IIIb/IV, open-label clinical trial of NIVO+IPI treatment in pts enrolled in a community practice setting with aRCC and a high unmet medical need. We present safety and efficacy results for the cohort of pts with aRCC of any histology and KPS 50%–60% from CheckMate 920 (NCT02982954). Methods: Pts with previously untreated advanced/metastatic RCC and KPS 50%–60% received NIVO 3 mg/kg + IPI 1 mg/kg Q3W × 4 doses followed by 480 mg NIVO Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 25 treated pts with KPS 50%–60%, 76% were men; median age was 67 years (range, 34–81). IMDC risk was favorable in 0%, intermediate in 32%, and poor in 68% of pts; 84% had clear cell and 16% had non-clear cell RCC histology. With a minimum follow-up of 25 months, median duration of therapy (95% CI) was 2.3 months (2.1–7.7) for NIVO and 2.1 months (2.1–2.1) for IPI. The median number of doses (range) received was 4 (1–27) for NIVO and 4 (1–4) for IPI; 76% of pts received ≥ 4 NIVO doses and 68% received all 4 IPI doses. The only grade 3–4 imAEs by category were hepatitis (4.0%) and adrenal insufficiency (4.0%). No grade 5 imAEs occurred. Overall, 4 (16%) pts discontinued due to any-grade adverse events (n = 1 each for elevated AST, malignant neoplasm progression, back pain, and acetabulum fracture). Of 18 evaluable pts, ORR was 33.3% (95% CI, 13.3–59.0); no pts had a complete response and 6 had partial response. Median time to objective response was 4.5 months (range, 2.5–24.7). Median duration of objective response was 20.6 months (range, 0.03+–24.2+). Median PFS was 4.6 months (95% CI, 2.5–14.8). Median OS was 15.6 months (95% CI, 5.3–25.1). Conclusions: NIVO+IPI demonstrated an acceptable safety profile and promising antitumor activity in pts with previously untreated aRCC and KPS 50%–60%. The combination was tolerated at a dose intensity similar to that observed in clinical trials conducted in pts with higher KPS (≥ 70%). These data support the value of NIVO+IPI in pts who may not be considered ideal candidates for this therapy and consequently may have limited treatment options. Clinical trial information: NCT02982954 .

Safety and efficacy of nivolumab plus ipilimumab (NIVO+IPI) in patients with advanced renal cell carcinoma (aRCC) with brain metastases: Interim analysis of CheckMate 920.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4517-4517 ◽  
Author(s):  
Hamid Emamekhoo ◽  
Mark Olsen ◽  
Bradley Curtis Carthon ◽  
Alexandra Drakaki ◽  
Ivor John Percent ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Antitumor Activity ◽  
Brain Metastases ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Immune Mediated ◽  
Grade 3

4517 Background: Previous clinical trials of patients (pts) with aRCC, including CheckMate 214, have mostly excluded pts with brain metastases. However, antitumor activity in pts with brain metastases has been observed in pts with melanoma treated with NIVO 1 mg/kg + IPI 3mg/kg and pts with non-small cell lung cancer treated with NIVO 240 mg + IPI 1mg/kg. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO + IPI treatment in pts with aRCC with a high unmet medical need. Here, we present the safety and efficacy interim results for the cohort of pts with brain metastases. Methods: Pts with previously untreated aRCC of any histology, with asymptomatic brain metastases (not on corticosteroids or receiving radiation), and Karnofsky performance status ≥70% were assigned to treatment with NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses, followed by NIVO 480 mg every 4 weeks. Pts were treated until disease progression, unacceptable toxicity, or for a maximum of 2 years. The primary endpoint was the incidence of high-grade immune-mediated adverse events (IMAEs). Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 per investigator. Exploratory endpoints included additional safety analyses and overall survival (OS). Results: Overall, 28 patients were enrolled in the brain metastases cohort. With a minimum follow-up of 6.47 months, grade 3-4 IMAEs within 100 days of last dose were reported in 6 cases. The grade 3-4 IMAEs observed in ≥ 1 patient were diarrhea, colitis, diabetic ketoacidosis, immune-mediated hepatitis, hypophysitis, and rash of any type (n = 1 each). No treatment-related grade 5 IMAEs were reported. ORR by RECIST v1.1 per investigator in all treated subjects was 28.6% (95% CI 13.2–48.7). Median PFS in all treated subjects was 9.0 months (95% CI 2.9–not estimable [NE]). Median OS has not been reached (95% CI 13.1–NE). Conclusions: In pts with aRCC and brain metastases who are often excluded from clinical trials, NIVO + IPI treatment showed a safety profile consistent with previous reports of this dosing regimen, with encouraging antitumor activity. Clinical trial information: NCT02982954.

Nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma (nccRCC): Safety and efficacy from CheckMate 920.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 309-309
Author(s):  
Scott S. Tykodi ◽  
Lucio N. Gordan ◽  
Robert S. Alter ◽  
Edward Arrowsmith ◽  
Michael Roger Harrison ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Collecting Duct ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Grade 3

309 Background: The long-term efficacy and tolerability of nivolumab (NIVO) 3 mg/kg + ipilimumab (IPI) 1 mg/kg Q3W × 4 doses followed by NIVO 3 mg/kg Q2W for previously untreated advanced RCC (aRCC) demonstrated in the registrational CheckMate 214 clinical trial was based on patients (pts) with a predominantly clear cell component. CheckMate 920 (NCT02982954) is a US community-based, multi-arm, phase IIIb/IV clinical trial of NIVO+IPI treatment in pts with previously untreated aRCC and clinical features mostly excluded from phase III trials. Here, we present the safety and efficacy results for the cohort of pts with nccRCC from CheckMate 920, a patient population with a poor prognosis and without a definitive effective treatment. Methods: Pts with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥ 70%, and any International Metastatic Renal Cell Database Consortium risk received NIVO 3 mg/kg + IPI 1 mg/kg (NIVO3+IPI1) Q3W × 4 doses followed by NIVO 480 mg Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of any-causality grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints: progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator), duration of response (DOR), and time to response (TTR). Exploratory endpoints included overall survival (OS). Results: Of 52 treated pts with nccRCC, 69.2% were men; median age was 64 years (range, 23–86), and 28.8% had sarcomatoid features. Histological subtypes were papillary (34.6%), chromophobe (13.5%), translocation associated (3.8%), collecting duct (3.8%), renal medullary (1.9%), or unclassified (42.3%). With 24.1 months minimum follow-up, median duration of therapy (range) was 3.5 months (0.0–25.8) for NIVO and 2.1 months (0.0–3.9) for IPI. Median (range) number of doses received was 4.5 (1–28) for NIVO and 4.0 (1–4) for IPI. No grade 5 imAEs occurred. Grade 3–4 imAEs (n = 52) by category were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). ORR (n = 46) was 19.6% (95% CI, 9.4–33.9). Two pts achieved complete response (papillary, n = 1; unclassified pathology, n = 1), 7 achieved partial response (papillary, n = 4; unclassified pathology, n = 3), and 17 pts had stable disease. Median TTR was 2.8 months (range, 2.1–4.8). Median DOR was not reached (range, 0.03+–27.8+); 8 of 9 responders remain without reported progression. Median PFS (n = 52) was 3.7 months (95% CI, 2.7–4.6). Median OS (n = 52) was 21.2 months (95% CI, 16.6–not reached). Conclusions: In pts with previously untreated nccRCC, a population with high unmet medical need, treatment with NIVO3+IPI1 Q3W followed by NIVO 480 mg Q4W showed no new safety signals, and encouraging antitumor activity. Clinical trial information: NCT02982954 .

Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and brain metastases: results from the CheckMate 920 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4515-4515
Author(s):  
Hamid Emamekhoo ◽  
Mark R Olsen ◽  
Bradley Curtis Carthon ◽  
Alexandra Drakaki ◽  
Ivor John Percent ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Safety And Efficacy ◽  
Medical Need ◽  
Grade 3

4515 Background: Combination therapy with nivolumab plus ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability in patients with previously untreated advanced renal cell carcinoma (aRCC). Previous phase 3 clinical trials of patients with advanced or metastatic cancers have mostly excluded patients with brain metastases. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO+IPI treatment in patients with aRCC with a high unmet medical need. We present updated safety and efficacy results for the cohort of patients with aRCC of any histology and brain metastases from CheckMate 920 (NCT02982954). Methods: Patients with previously untreated advanced/metastatic aRCC of any histology, with asymptomatic brain metastases (not currently receiving corticosteroids or radiation), and Karnofsky performance status ≥ 70% were assigned to treatment with NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks × 4 doses followed by NIVO 480 mg every 4 weeks for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 28 treated patients with brain metastases, 85.7% were men; median (range) age was 60 (38–87) years, and 14.3% had sarcomatoid features. With 24.5 months minimum follow-up of the 28 patients enrolled, median duration of therapy (range) was 3.4 (0.0–23.3) months for NIVO and 2.1 (0.0–3.3) months for IPI. No grade 5 imAEs occurred. Grade 3–4 imAEs by category were diarrhea/colitis (7.1%), hypophysitis (3.6%), rash (3.6%), hepatitis (3.6%), and diabetes mellitus (3.6%). Of the 25 patients who were evaluable for ORR, the ORR was 32.0% (95% CI, 14.9–53.5). No patients achieved complete response, 8 achieved partial response, and 10 patients had stable disease. Median time to response (range) was 2.8 (2.4–3.0) months. Median duration (range) of response was 24.0 (3.9–not estimable [NE]) months; 4 of 8 responders remain without reported progression. Of 28 patients, 7 (25%) had intracranial progression. Median PFS (n = 28) was 9.0 (95% CI, 2.9–12.0) months. Median OS (n = 28) was still not reached (95% CI, 14.1 months–NE). Conclusions: In patients with previously untreated aRCC and brain metastases, a population with high unmet medical need that is often underrepresented in clinical trials, the approved treatment regimen of NIVO+IPI followed by NIVO for aRCC showed no new safety signals and continues to show encouraging antitumor activity with longer follow-up. Clinical trial information: NCT02982954.

Retrospective Review of Safety and Efficacy of Anlotinib in Advanced Osteosarcoma With Metastases After Failure of Standard Multimodal Therapy

2021 ◽  
Author(s):  
Hanqing Li ◽  
Yang Li ◽  
Lei Song ◽  
Qiuchi Ai ◽  
shuai zhang
Keyword(s):  
Adverse Events ◽  
Multimodal Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Common Drug ◽  
Grade 3 ◽  
Therapeutic Doses

Abstract To study and observe the safety and efficacy of anlotinib in the treatment of advanced osteosarcoma with metastases. We retrospectively studied patients with advanced osteosarcoma and metastases who received anlotinib treatment in our hospital from June 2018 to April 2020. All patients had received standard multimodal therapies, before taking anlotinib. Therapeutic doses of anlotinib were 12 mg for adults and 10 mg for children and adolescents once a day for 2 consecutive weeks, followed by a week of withdrawal. This 3-week cycle of treatment was continued until the tumor progressed rapidly or the patients failed to tolerate the side effects. Adverse drug reactions were recorded, and therapeutic efficacy was evaluated based on progression free survival (PFS), disease control rate (DCR), overall survival (OS), and objective response rate (ORR). The median PFS was 9.81 ± 0.9 months, and the 6-month and 10-month PFS rates were 73.3% and 33.3%, respectively. The median OS was 11.43 ± 0.58 months. No patients achieved complete response. After 6 months of treatment, the DCR and ORR were 80% and 13.3%, respectively. No drug-related deaths or Grade 4 adverse events occurred in the patients. Five patients (33.3%) had Grade 3 adverse events. The most common drug-related adverse events were hand-food syndrome, fatigue, high blood pressure, anorexia, and pneumothorax. Anlotinib had a certain curative effect on patients with advanced osteosarcoma and metastases after failure of standard treatment. The adverse events were mostly tolerable or relieved after treatment.

A multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) who do not meet eligibility criteria for clinical trials.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 353-353 ◽  
Author(s):  
Daniel Yick Chin Heng ◽  
Toni K. Choueiri ◽  
Jae-Lyun Lee ◽  
Lauren Christine Harshman ◽  
Georg A. Bjarnason ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Exclusion Criteria ◽  
Eligibility Criteria ◽  
Number Of Patients

353 Background: Clinical trials have strict eligibility criteria to maintain internal validity. These criteria exclude many patients to whom the trial results are later applied to in clinical practice. Patients that do not meet eligibility criteria are poorly characterized. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) < 70%, brain metastases, non-clear cell histology, hemoglobin ≤ 9 g/dL, creatinine > 2x the upper limit of normal, platelet count of < 100x103/uL, neutrophil count < 1500/mm3 or corrected calcium ≤ 12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p < 0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p = 0.0074). When adjusted by the Heng et al prognostic categories, the hazard ratio for death between trial ineligible vs trial eligible patients was 1.621 (95% CI = 1.431–1.836, p < 0.0001). If only KPS, brain metastases and non-clear cell histology were used as exclusion criteria, 672 (32%) patients were excluded and the results were similar. Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Designing more inclusive clinical trials for this “ineligible” patient population are needed. [Table: see text]

A randomized phase II trial comparing different schedules of nab-paclitaxel (nabP) combined with gemcitabine (GEM) as first line treatment for metastatic pancreatic adenocarcinoma (mPDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4100-4100 ◽  
Author(s):  
Philippa Corrie ◽  
Wendi Qian ◽  
Bristi Basu ◽  
Juan W. Valle ◽  
Stephen Falk ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Age Range

4100 Background: NabP+GEM chemotherapy improves survival compared with GEM monotherapy as treatment for mPDAC. A PDAC mouse model suggested that nabP potentiates GEM activity by reducing cytidine deaminase levels and scheduling may be critical to optimise clinical benefit. Methods: Patients (pts) were randomised to receive standard concomitant (CON) nabP+GEM or sequential (SEQ) administration, with nabP given 24 hours before GEM. After 6 cycles, pts benefiting from treatment could continue the same regimen until disease progression. The primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints included safety, objective response rate (ORR), overall survival (OS) and quality of life (QoL). Serial blood and baseline tumour samples were collected for exploratory biomarkers. Results: Between March 2014 and 2016, 146 pts (71 SEQ, 75 CON) were recruited. Median age (range) was 66 (45-82) years; Karnofsky performance status was 70 (in 12% pts), 80 (27%), 90 (38%) or 100 (24%); 47% had pancreatic head primaries; 84% had liver metastases. Median no. cycles received was 4 SEQ, 3 CON; 51 pts (35%) received ≥6 cycles of treatment (42% SEQ, 28% CON). A 24+2hr interval was achieved in > 90% SEQ admin. Grade ≥3 adverse events experienced by ≥10% pts (SEQ, CON) were neutropaenia (54%, 30%; p = 0.003), febrile neutropaenia (12%, 12%), fatigue (22%, 15%), vomiting (7%, 11%) and anaemia (10%, 5%). G-CSF was administered at local investigator's discretion to 35 pts (23 SEQ, 12 CON; p = 0.015). To date, 112 pts have died. 6 month (m) PFS by SEQ and CON arms were 47% and 33%; median PFS were 5.8 and 4.0m; hazard ratio (HR) = 0.66, 95% CI = 0.46-0.95; 12m OS by SEQ and CON arms were 29% and 26%; median OS were 10.1 and 7.9m; HR = 0.88, 95% CI = 0.61-1.29. ORR was 50% SEQ and 33% CON (p = 0.065). Mean baseline QoL Global health status score was 60.6 SEQ and 63.4 CON. The mean change in QoL score from baseline at 24 weeks was -2.1 SEQ and -12.1 CON. Conclusions: Sequential delivery of nabP combined with GEM trended towards improving all clinically relevant efficacy end points: PFS, OS, and ORR. Translational correlates will be reported in due course. Clinical trial information: ISRCTN71070888.

Clinical outcomes by nephrectomy status in METEOR, a randomized phase 3 trial of cabozantinib (cabo) vs everolimus (eve) in patients (pts) with advanced renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
Nizar M. Tannir ◽  
Thomas Powles ◽  
Bernard J. Escudier ◽  
Frede Donskov ◽  
Viktor Grünwald ◽  
...  
Keyword(s):  
Risk Group ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Palliative Therapy ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Phase 3 ◽  
Grade 3 ◽  
To Receive

4570 Background: Most pts with advanced RCC undergo nephrectomy (Nx) as curative or palliative therapy. In a retrospective analysis of pts treated with targeted therapy, pts who were older and had more comorbidities and higher tumor grade were less likely to have had Nx. Pts without Nx had shorter overall survival (OS) than pts with Nx (Hanna, J Clin Oncol 2016). Here we report outcomes for cabo vs eve in pts with advanced RCC with or without prior Nx in the phase 3 METEOR trial (NCT01865747). Methods: 658 pts with clear cell RCC and ≥1 prior VEGFR TKI were randomized 1:1 to receive cabo at 60 mg qd or eve at 10 mg qd. Stratification was by MSKCC risk group and number of prior VEGFR TKIs. Endpoints included progression-free survival (PFS), OS, and objective response rate (ORR). Results: 85% of enrolled pts had prior Nx of which 7% were partial; 15% had no prior nephrectomy (NoNx). Baseline characteristics, including Karnofsky performance status (KPS), MSKCC risk group, time from diagnosis to randomization, and median sum of diameters (SoD) for tumor target lesions, were less favorable for the NoNx subgroup (Table). Improved PFS and OS with cabo vs eve were observed regardless of Nx status. For the Nx subgroup, the hazard ratio (HR) was 0.51 (95% CI 0.41-0.64) for PFS and 0.66 (95% CI 0.52-0.84) for OS; for the NoNx subgroup, the HR was 0.51 (95% CI 0.30-0.86) for PFS and 0.75 (95% CI 0.44-1.27) for OS. Median OS was longer in the Nx subgroup for both treatment arms (Table). ORR per independent radiology committee (IRC) for cabo vs eve was 17% vs 4% for Nx and 21% vs 2% for NoNx. Grade 3 or 4 adverse events for both subgroups were generally consistent with the safety profiles of cabo and eve in the overall population. Conclusions: Cabo improved PFS, ORR, and OS compared with eve in pts with advanced RCC irrespective of nephrectomy status. Clinical trial information: NCT01865747. [Table: see text]

Phase 3 KEYNOTE-426 trial: Pembrolizumab (pembro) plus axitinib versus sunitinib alone in treatment-naive advanced/metastatic renal cell carcinoma (mRCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4597-TPS4597 ◽  
Author(s):  
Brian I. Rini ◽  
Thomas Powles ◽  
Mei Chen ◽  
Markus Puhlmann ◽  
Michael B. Atkins
Keyword(s):  
Adverse Events ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Risk Category ◽  
Antiangiogenic Agents ◽  
Phase 3 ◽  
End Points ◽  
Patient Reported ◽  
Treatment Naïve

TPS4597 Background: Antiangiogenic agents, including sunitinib and axitinib, have shown clinically significant efficacy in patients (pts) with mRCC. Results from a phase 1b study in 52 pts suggest first-line pembro, an anti–programmed death 1 antibody, in combination with axitinib, has substantial antitumor activity in mRCC (objective response rate [ORR], 71%) and manageable toxicity. The phase 3, multicenter, open-label, randomized KEYNOTE-426 study (NCT02853331) is designed to evaluate the efficacy and safety of pembro plus axitinib versus sunitinib alone in pts with treatment-naive mRCC. Methods: Key eligibility criteria include age ≥18 years, histologically confirmed mRCC with clear cell component (with or without sarcomatoid features), measurable disease (RECIST v1.1, investigator review), no prior systemic therapy for advanced disease, Karnofsky performance status ≥70%, and provision of a tumor sample for biomarker analyses. Before randomization, pts will be stratified by International Metastatic RCC Database Consortium risk category and geographic region. 840 pts will be randomly assigned 1:1 to receive pembro 200 mg every 3 wk + axitinib 5 mg twice daily or sunitinib 50 mg once daily for 4 wk followed by 2 wk off. Treatment will continue until progressive disease, unacceptable adverse events (AEs), or withdrawal of consent. Pts in the pembro arm may receive up to 35 doses of pembro, after which axitinib-only treatment may continue. Imaging will be performed at wk 12, then every 6 wk for the first year, and every 12 wk thereafter. Bone scans will be performed at baseline, and if positive, repeated at wk 18, 30, 42, and 54, and every 24 wk thereafter. AEs will be monitored throughout and graded per National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Primary end points are to compare progression-free survival (RECIST v1.1, central review) and overall survival between treatment arms. Secondary end points include the comparison of ORR, duration of response, disease control rate, safety, and patient-reported outcomes between arms. Enrollment is ongoing. Clinical trial information: NCT02853331.

Randomized multicenter trial of 3 weekly cabazitaxel versus weekly paclitaxel chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (MBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1008-1008
Author(s):  
Amit Bahl ◽  
Jeremy Braybrooke ◽  
Alicia Bravo ◽  
Emily Foulstone ◽  
Jessica Ball ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Performance Status ◽  
Objective Response ◽  
Significant Risk ◽  
Weekly Paclitaxel ◽  
First Line ◽  
Patient Reported ◽  
Grade 3 ◽  
Line Chemotherapy

1008 Background: Paclitaxel is commonly used as first line chemotherapy for HER2 negative MBC. However, with response rates of 21.5-53.7% and a significant risk of peripheral neuropathy there is a need for more effective and better tolerated chemotherapy (CCT). Methods: This open label randomised (1:1) phase 2 trial compared 6 cycles of cabazitaxel (25 mg/m2) every 3 weeks, with weekly paclitaxel (80mg/m2) over 18 weeks as first line CCT. HER2 negative and performance status ≤1 patients were eligible. Patients on cabazitaxel received GCSF prophylaxis. Primary endpoint was Progression Free Survival (PFS) with 127 events required to detect a hazard ratio (HR) of 0.65 with 85% power. Secondary endpoints included objective response rate (ORR; RECIST 1.1), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). Results: 158 patients were recruited from 14 UK hospitals (79 in each arm). Median age (range) was 56(34-81) in the cabazitaxel arm and 61(34-79) in the paclitaxel arm. 61% of patients were performance status 0. Median time on treatment was 15 weeks for both arms, but more patients on paclitaxel had a treatment delay (61% vs 39%) or dose reduction (37% vs 24%). Comparing cabazitaxel to paclitaxel after 146 PFS events, median PFS was 6.7 vs 5.8 months (HR 0.84; 95%CI 0.60–1.18, P = 0.3). There was no difference in OS, median 19.3 vs 20.0 months (HR 0.94; 95%CI 0.63-1.40, P = 0.7), ORR (42% vs 37%) or TTR (HR 1.09; 95%CI 0.68–1.74, P = 0.7). Grade ≥3 adverse events occurred in 42% of patients on cabazitaxel and 48% on paclitaxel. Diarrhoea, febrile neutropenia and nausea were the most common grade ≥3 events in the cabazitaxel arm with rates of 11%, 11% and 10% respectively compared to 1%, 1% and 0% in the paclitaxel arm. In the paclitaxel arm the top grade ≥3 events were lung infection and peripheral neuropathy, 6% and 5% respectively compared to 2.5% and 0% in the cabazitaxel arm. Peripheral neuropathy of any grade was reported by 55% of patients treated with paclitaxel vs 17% on cabazitaxel. Alopecia occurred in 41% of patients on paclitaxel compared to 27% on cabazitaxel. Adverse events leading to discontinuation were more frequent with paclitaxel (22%) than cabazitaxel (14%). Over the course of treatment, mean EQ5D single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in the cabazitaxel arm compared to paclitaxel suggestive of better QoL on Cabazitaxel. Conclusions: 3 weekly cabazitaxel as first line chemotherapy in HER2 negative MBC does not significantly improve PFS compared to weekly paclitaxel, though it has a lower risk of peripheral neuropathy with better patient reported overall health outcomes. Cabazitaxel is safe and well tolerated for MBC and requires fewer hospital visits, an important consideration in the COVID pandemic and beyond. Clinical trial information: NCT03048942 .

Randomized phase II clinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8071-8071 ◽  
Author(s):  
P. Zatloukal ◽  
D. S. Heo ◽  
K. Park ◽  
J. Kang ◽  
C. Butts ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Grade 3

8071 Background: Pts diagnosed with advanced NSCLC with good performance status typically receive platinum-based chemotherapy; however, no approved maintenance therapy exists. Tremelimumab, a fully human anti-CTLA4 mAb, is associated with durable responses in some pts with metastatic melanoma. Methods: This open-label, randomized, multicenter, phase II clinical trial evaluating efficacy and safety of tremelimumab as maintenance therapy was conducted in pts with locally advanced or metastatic NSCLC with ECOG performance status ≤1. Pts treated with ≥4 cycles of first-line platinum-based therapy resulting in either stable disease (SD) or response per RECIST were eligible and were randomized 3–6 weeks after prior therapy. Pts received 15 mg/kg IV tremelimumab Q90D or BSC until disease progression. Primary endpoint was progression-free survival (PFS) at 3 months. Secondary endpoints included safety, objective response rate, and 1-year survival. Results: Eighty-seven pts received tremelimumab (n=44) or BSC (n=43). Nine (20.9%; 90% CI: 11.4%, 33.7%) pts receiving tremelimumab and 6 (14.3%; 90% CI: 6.4%, 26.3%) pts receiving BSC were progression free at 3 months. Among pts receiving tremelimumab, there were 2 (4.8%) partial responses and 7 (16.6%) SDs, compared with 0 and 6 (14.3%) pts receiving BSC, respectively. Treatment-related adverse events (AEs) were observed in 27 (61.4%) pts receiving tremelimumab and 3 (7.0%) receiving BSC. Nine pts (20.5%) receiving tremelimumab reported grade 3 or 4 AEs compared with 0 patients receiving BSC. The most common grade 3 or 4 AEs attributed to tremelimumab were diarrhea and colitis (n=4, 9.1%). Conclusions: In pts with advanced NSCLC and good performance status receiving platinum-based first-line therapy, single-agent tremelimumab was tolerable, with safety consistent with prior studies. Although PFS analysis did not demonstrate superiority of tremelimumab over BSC, the 4.8% objective response rate seen only in the investigational arm may support future combination studies. Analysis of 1-year survival is forthcoming. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document