Safety of weight-based dosing of nivolumab with or without ipilimumab by body mass index (BMI) stratified by sex across 14 CheckMate clinical trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15114-e15114
Author(s):  
Jennifer Leigh McQuade ◽  
Hans J. Hammers ◽  
Helena Furberg ◽  
Andreas Engert ◽  
Thierry Andre ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Smoking Status ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Female Patients ◽  
Grade 3 ◽  
Risk Prognosis ◽  
Tumor Types ◽  
Obesity And Cancer ◽  
The Impact

e15114 Background: Associations between obesity and cancer risk, prognosis, and therapeutic outcomes have been extensively researched. However, the impact of BMI on safety in patients receiving immunotherapy has not been well described. Methods: A descriptive, retrospective analysis examined associations between BMI (kg/m2) (underweight/normal, BMI < 25; overweight, 25 ≤ BMI < 30; obese, BMI ≥ 30) and incidence of any-grade and grade 3/4 immune-mediated adverse events (imAEs) in patients receiving ≥ 1 dose of nivolumab 3 mg/kg as monotherapy (NIVO3; n = 2746). Data were pooled from CheckMate clinical trials across 8 tumor types. Data from nivolumab in combination with ipilimumab cohorts (n = 1026) and safety analyses by specific imAEs and tumor types will be presented. Results: Select NIVO3 monotherapy cohort patient demographics were: 68.5% male, median age of 61 years, median 10 doses received, and median BMI of 25.3 kg/m2. Results showed a trend towards higher incidence of any-grade, but not grade 3/4, imAEs in obese vs overweight and obese vs underweight/normal BMI patients (Table). BMI associations with imAE incidence were consistent with the overall trend across pre-defined subsets, including smoking status, age, and ECOG performance status. Both male and female patients had an increased incidence of any-grade imAEs with obesity; however, obese female patients had a higher incidence of grade 3/4 imAEs vs underweight/normal BMI (Table). Conclusions: This was a novel analysis of BMI and safety in 2746 patients across 8 tumor types in CheckMate clinical trials who were treated with nivolumab monotherapy. While obese patients showed a trend towards higher incidence of any-grade imAEs than those with overweight and underweight/normal BMI, incidence of grade 3/4 imAEs was consistent across BMI categories. Clinical trial information: CheckMate 017,026,057,025,039,205,040,066,067,141,275,142,016,214 (NCT numbers do not fit in field) . [Table: see text]

A phase I clinical study of biweekly carboplatin and gemcitabine in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12024-12024
Author(s):  
P. Kumar ◽  
M. Keshtgarpour ◽  
H. Kumar ◽  
A. Dudek
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Hematological Toxicity ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Tumor Types ◽  
Dose Levels

12024 Background: Carboplatin (CBDCA) and gemcitabine (GEM) in combination is used commonly in lung cancer and is administered on a 21 day cycle. The purpose of this study was to determine the maximum tolerated dose (MTD) of CBDCA and GEM administered on a biweekly schedule and to assess safety and efficacy of this schedule. Methods: GEM was given intravenously (IV) over 30 minutes followed by CBDCA also given IV over 30 minutes. This combination was given on day 1 every 2 weeks. The dose levels examined are shown in the Table . A total of 26 patients were studied (18 male, 8 female) with median age of 56 (range 41–83 years); ECOG performance status of 24 patients were 0 (5), 1 (16), 2 (2), 3 (1); prior chemotherapy ranged from 0 to 4 regimens; median number of cycles administered per patient was 3 (range 1–9) with a total of 81 cycles. The primary tumors were lung (11), melanoma (4), head and neck (3), squamous cell penile/toe (2), bladder (2), kidney (1), gastric (1), esophageal (1) and ovary (1). Results: No DLTs were seen in any of these patients and the MTD was not reached. Delay in treatment was seen in total of 6 cycles due to myelosuppression and 1 cycle due to nausea and anorexia. Grade 3/4 hematological toxicity rates: anemia - 3/81 cycles (3.7%), neutropenia - 20/81 cycles (25%), and thrombocytopenia - 4/81 cycles (5%). Non-hematological toxicity was mild. The median time to progression was 40 days (range 4–133) and of 18 evaluable patients partial response or stable disease was seen in 7 (38.8%). Conclusions: Even at maximum tested dose of GEM at 2000 mg/m2 and CBDCA at AUC of 3.0, this schedule is well tolerated. Hematological toxicity such as neutropenia and thrombocytopenia was minimal. We plan to study this schedule of GEM and CBDCA in appropriate tumor types in combination with biologic agents. [Table: see text] [Table: see text]

A phase II study of capecitabine and oxaliplatin (CAPOX) in metastatic adenocarcinoma of the small bowel (SBA) or ampulla of Vater

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14025-14025
Author(s):  
M. J. Overman ◽  
S. Chedid ◽  
J. Morris ◽  
S. Waldrum ◽  
R. A. Wolff
Keyword(s):  
Small Bowel ◽  
Performance Status ◽  
Complete Response ◽  
Ampulla Of Vater ◽  
Ecog Performance Status ◽  
Ampullary Adenocarcinoma ◽  
Highly Active ◽  
Common Grade ◽  
Grade 3 ◽  
Tumor Types

14025 Background: Metastatic SBA and ampullary adenocarcinoma (AAC) are incurable, aggressive malignancies. Limited data exists regarding the role of systemic chemotherapy in these diseases. Given the marked activity of CAPOX in other cancers of the gastrointestinal tract, we have investigated the activity of this combination in these two tumor types. Methods: Patients (pts) with either metastatic or unresectable SBA and AAC who had adequate organ function, ECOG performance status (PS) ≤2 and measurable disease per modified RECIST criteria were enrolled. Prior use of 5-FU or capecitabine as adjuvant therapy, neoadjuvant therapy, or with radiation was allowed. CAPOX was administered as a 21 day cycle with oxaliplatin 130mg/m2 IV on day 1 and capecitabine 750mg/m2 PO BID days 1–14. Up to 30 pts will be enrolled. The primary endpoint is overall response rate (ORR). Results: Eleven pts have been enrolled from 11/04 to 12/05 (6 with AAC and 5 with SBA). Ten pts have received ≥2 cycles and are evaluable for response. All pts had metastatic disease and none had received prior chemotherapy. Patient (pt) characteristics: median age 59 (49–76); M/F (4/7); 91% PS 0–1. Grade 3/4 toxicities included fatigue (5), neuropathy (1), anorexia (1), thrombocytopenia (1), hypokalemia (1), hyponatremia (1), and musculoskeletal (1). Common grade 1/2 toxicities included neuropathy (8), nausea (8), diarrhea (6), and fatigue (5). Four pts required dose reduction and 1 pt discontinued due to toxicity (grade 3 fatigue). Six pts, 3 AAC and 3 SBA, responded with an ORR of 60% (95% CI 31 to 83%). Five responses have been confirmed and 1 AAC pt obtained a complete response after 5 cycles of treatment. Median time to progression was 6.8m (95% CI 4.4 to 9.3+m). Conclusions: The combination of CAPOX is both well-tolerated and highly active. The ORR of 60% is one of the highest yet reported in the literature for the treatment of adenocarcinoma of the small bowel and ampulla of Vater. Enrollment continues on this trial. (Supported by a research grant from Sanofi-Aventis). [Table: see text]

Clinical outcomes and safety in men ≥ 75 and < 75 years with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in the phase 3 PREVAIL trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Julie Nicole Graff ◽  
Giulia Baciarello ◽  
Andrew J. Armstrong ◽  
Celestia S. Higano ◽  
Peter Iversen ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Age Groups ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Treatment Safety ◽  
The Impact

200 Background: In the phase 3 PREVAIL trial, enzalutamide (ENZA), an androgen receptor inhibitor, improved overall survival (OS) and radiographic progression-free survival (rPFS) relative to placebo (PBO) in chemotherapy-naïve men with mCRPC. Methods: PREVAIL randomized 1,717 patients (pts) with asymptomatic or minimally symptomatic chemotherapy-naïve mCRPC 1:1 to ENZA 160 mg daily or PBO. Coprimary endpoints were OS and rPFS. This prespecified analysis evaluated the impact of age (≥ 75 vs < 75 years) on efficacy and safety. Results: In PREVAIL, 609 (35%) pts were aged ≥ 75 years. This older subset had several poorer baseline prognostics relative to those aged < 75 years: worse ECOG performance status (ECOG 1: 45.0% vs 24.7%), higher prostate-specific antigen (PSA; 73.3 vs 37.3 ng/mL) and more cardiovascular disease (26.9% vs 16.5%). In both older and younger pts, ENZA improved OS, rPFS and time to PSA progression (Table). Pts aged ≥ 75 years in both the ENZA and PBO groups combined had a higher rate of grade ≥ 3 adverse events (46% vs 37% in younger pts) and among enzalutamide-treated men more older pts reported falls (any grade; ENZA 19% and PBO 8%) than younger pts (ENZA 7% and PBO 4%). Fewer pts ≥ 75 years received subsequent antineoplastic therapies. Conclusions: In PREVAIL, efficacy outcomes in elderly (≥ 75 years) and younger (< 75 years) pts with chemotherapy-naïve mCRPC were comparable and pts consistently benefited from ENZA treatment. Safety with ENZA was similar in both age groups, although older pts reported a higher incidence of falls and received fewer subsequent antineoplastic therapies. Clinical trial information: NCT01212991. [Table: see text]

Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19266-e19266
Author(s):  
Igor I. Rybkin ◽  
Nadia Z Haque ◽  
Kristen Collins ◽  
Louisa Laidlaw ◽  
Tom Mikkelsen
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Performance Status ◽  
Tumor Board ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Ecog Performance Status ◽  
Off Label ◽  
Molecular Tumor Board ◽  
The Impact

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.

Safety and efficacy of apatinib as third or later line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma: A post-marketing phase IV study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Jin Li ◽  
Shukui Qin ◽  
Lu Wen ◽  
Junsheng Wang ◽  
Wenying Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Line Treatment ◽  
Ecog Performance Status ◽  
Safety And Efficacy ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Grade 3 ◽  
Phase Iv

e16034 Background: Apatinib, a small molecule multi-target tyrosine kinase inhibitor with high selectivity for VEGFR-2, has been approved for the treatment of advanced gastric cancer or gastroesophageal adenocarcinoma in China by significantly improving progression-free survival (PFS) and overall survival (OS). Here, we report safety and efficacy data from an open-label, single-arm, multicenter, phase IV trial of apatinib as a third-line or later line treatment for advanced gastric cancer. Methods: Eligible patients had histologically or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate haematological and hepatic function; and failure of at least two lines of chemotherapy. Patients received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included PFS and OS. Results: The intention-to-treat population (ITT) included 2004 patients. At baseline, the median age was 59 (range, 19-85) years, ECOG performance status of 0/1/2 (%) was 15.4/68.8/15.1, and stage III/IV was 3.5/96.4; 98.8% had metastases, and among which metastatic foci≤2/ > 2 was 64.5/34.2 (%), respectively. 89.6% of the patients were given apatinib 500mg as the initial does and the median treatment duration was 56 days. After a median follow-up of 126.5 days, adverse events (AEs) occurred in 95.1% of the patients and 70.3% were grade ≥3. 87.9% of the patients experienced treatment-related AEs (TRAEs), of which 51% had grade ≥3, 12.3% and 16.8% reduced dose and discontinued the treatment, respectively. 57 (2.9%) TRAEs-related deaths were reported, mainly because of gastrointestinal bleeding (16 cases), upper gastrointestinal haemorrhage (7), cerebral haemorrhage (2), and gastric perforation (1). The incidence of TRAEs of special interest was 74.3%; 38.1% of patients developed grade≥3, mainly including hypertension (26.3%), bleeding (5.1%), proteinuria (4.5%), and hand-foot syndrome (3.1%). In an ITT population, median PFS was 2.7 months (95%CI 2.23-2.79) and median OS was 5.8 months (95% CI 5.42-6.11). Conclusions: This study confirms that apatinib has a well-established and manageable safety profile and survival benefit as third or later line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma. Clinical trial information: NCT02426034.

Model-based analysis to support dose selection of pevonedistat (PEV) combined with azacitidine (AZA) in patients (pts) with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7042-7042
Author(s):  
Xiaofei Zhou ◽  
Diane R. Mould ◽  
Dan Zhao ◽  
Mikkael A. Sekeres ◽  
Lionel Adès ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Phase 1 ◽  
Performance Status ◽  
Disease Type ◽  
International Prognostic Scoring System ◽  
Population Pharmacokinetic ◽  
Starting Dose ◽  
Grade 3 ◽  
The Impact ◽  
Dose Reductions

7042 Background: PEV+AZA has been studied in higher-risk MDS/CMML and AML, with encouraging efficacy and an acceptable safety profile without added myelosuppression. This pooled analysis was performed to evaluate the impact of PEV exposure on safety and efficacy. Methods: Data from three studies (NCT01814826, NCT02782468 and NCT02610777) were used in the PEV exposure–safety analyses, including ≥ grade 3 neutropenia (NEU3), febrile neutropenia (FN), ≥ grade 3 thrombocytopenia, ≥ grade 3 alanine aminotransferase elevation, ≥ grade 3 aspartate aminotransferase elevation and ≥ grade 3 treatment-emergent adverse event (TEAE3), in pts with higher-risk MDS/CMML and AML who received PEV+AZA. Data from NCT02610777 were used for exposure–efficacy analyses, including overall survival (OS), event-free survival (EFS), complete response (CR) and CR+partial response (PR), in pts with higher-risk MDS/CMML who received PEV+AZA. The exposure metrics for individual pts were derived from a previously developed population pharmacokinetic model with pooled data from eight phase 1/2 studies. PEV exposure–safety relationships for the toxicity endpoints, exposure–CR and exposure–CR+PR, were estimated by logistic regression. Age, sex, race, baseline Eastern Cooperate Oncology Group (ECOG) Performance Status score and disease type were evaluated as covariates. Cox proportional-hazards models were used to evaluate the PEV exposure–survival for higher-risk MDS/CMML, with age, sex, baseline ECOG PS score, Revised International Prognostic Scoring System score (IPSS-R) and disease type as potential covariates. Results: In total, 135 pts (median age, 74 years; male, 64%; Caucasian, 82%) and 41 pts (median age, 74 years; male, 76%; Caucasian, 90%; median IPSS-R, 5.5) were included in PEV exposure–safety and exposure–efficacy analyses, respectively. PEV exposure was significantly related to the incidence of NEU3 ( p = 0.003), FN ( p = 0.02) and TEAE3 ( p = 0.02), supporting PEV dose reductions for pts with treatment-related toxicities. Relationships between PEV exposures and CR, CR+PR, EFS or OS indicated consistent clinical benefit across ranges of PEV exposure following a starting dose of 20 mg/m2. Conclusions: The association between exposure and safety supports PEV dose reductions for pts with treatment-related toxicities. The exposure–efficacy analyses indicated consistent clinical benefit across ranges of PEV exposure following a starting dose of 20 mg/m2. These results support a favorable benefit–risk profile of the 20 mg/m2 PEV dose on days 1, 3 and 5 in combination with AZA 75 mg/m2 for 7 days in 28-day cycles. Clinical trial information: NCT01814826 , NCT02782468 , NCT02610777.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 359-359
Author(s):  
Emeline Colomba ◽  
Ronan Flippot ◽  
Cécile Dalban ◽  
Sylvie Negrier ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Modulation ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Population Based ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Grade 3 ◽  
The Impact

359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.

Phase 3 comparison of high-dose once-daily (QD) thoracic radiotherapy (TRT) with standard twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC): CALGB 30610 (Alliance)/RTOG 0538.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8505-8505
Author(s):  
Jeffrey A Bogart ◽  
Xiaofei F. Wang ◽  
Gregory A. Masters ◽  
Junheng Gao ◽  
Ritsuko Komaki ◽  
...  
Keyword(s):  
Regional Lymph Node ◽  
Performance Status ◽  
Lymph Node Involvement ◽  
High Dose ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Once Daily ◽  
Concomitant Boost ◽  
Significant Difference ◽  
Grade 3

8505 Background: Although level 1 evidence is lacking, the majority of patients (pts) with LSCLC are treated with a high dose QD TRT regimen in clinical practice. CALGB 30610/RTOG 0538 was designed to determine if administering high dose TRT would improve overall survival (OS), compared with standard 45 Gy BID TRT, in LSCLC pts treated with chemoradiotherapy. Methods: Eligible pts had LSCLC, ECOG performance status (PS) 0-2 and regional lymph node involvement excluding contralateral hilar or supraclavicular nodes. This phase 3 trial was conducted in 2 stages. In the first stage, pts were randomized 1:1:1 to 45 Gy BID over 3 weeks, 70 Gy QD over 7 weeks, or 61.2 Gy concomitant boost (CB) over 5 weeks. For the second stage, the study planned discontinuation of one high dose arm based on interim toxicity analysis with patients then randomized 1:1 in the two remaining arms. TRT was given starting with either the 1st or 2nd (of 4 total) chemotherapy cycles. The primary endpoint was OS measured from date of randomization. Results: The trial opened 03/15/2008 and closed 12/01/2019 upon completing accrual, with the CB arm discontinued 3/11/2013 after interim analysis. This analysis includes 638 pts randomized to 45 Gy BID TRT (n = 313) or 70 Gy QD TRT (n = 325). Median age was 63 years (range 37-81), the majority of pts were Caucasian (86%), female (52%), and with ECOG PS 0-1 (95%). After median follow-up of 2.84 years (IQR:1.35 -5.61) for surviving pts, QD compared to BID did not result in a significant difference in OS (HR 0.94, 95% CI: 0.76-1.2, p = 0.9). Median, 2- and 4-year OS for QD were 30.5 months (95% CI: 24.4-39.6), 56% (95% CI: 0.51-0.62), and 39% (95% CI: 0.33-0.45), and for BID 28.7 months (95% CI: 26.2-35.5), 59% (95% CI: 0.53-0.65), and 35% (95% CI: 0.29-0.42). QD also did not result in a significant difference in PFS (HR 0.96, 95% CI: 0.78-1.18, p = 0.94). Most grade 3+ hematologic and non-hematologic adverse events (AEs) were similar between cohorts. Rates of grade 3+ febrile neutropenia, dyspnea, esophageal pain and dysphagia for QD were 12.6%,7%, 11.6% and 11.3%, and for BID 13.6%, 4%, 11.2 % and 9.5%. Grade 5 AEs were reported in 3.7% and 1.7% of the QD and BID cohorts, respectively. Results will be updated at presentation. Conclusions: High dose QD TRT to 70 Gy did not significantly improve OS compared with standard 45 Gy BID TRT. Nevertheless, favorable outcomes on the QD arm provide the most robust evidence available supporting high dose once-daily TRT as an acceptable option in LSCLC. Outcomes from this study, the largest conducted in LSCLC to date, will help guide TRT decisions for this patient population. Support: U10CA180821, U10CA180882; Clinical trial information: NCT00632853.

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 .

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