scholarly journals 349 Tolerability of tivozanib vs. sorafenib in elderly and/or immunotherapy-pretreated patients with metastatic renal cell cancer (mRCC) in TIVO-3

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A376-A376
Author(s):  
Vijay Kasturi ◽  
Bernard Escudier ◽  
Brian Rini ◽  
Sumanta Pal ◽  
David McDermott ◽  
...  
Keyword(s):  
Renal Cell ◽  
Drug Exposure ◽  
Cell Cancer ◽  
Age Groups ◽  
Progression Free Survival ◽  
List Type ◽  
Class Effect ◽  
Open Label ◽  
Grade 3 ◽  
Dose Reductions

BackgroundThe TIVO-3 trial demonstrated improved progression-free survival (PFS) with TIVO when compared to sorafenib (SOR; 5.6 mo. vs 3.9 mo., respectively; HR 0.73) and better tolerability with reduced need for dose interruptions (p = 0.0164), dose reductions (p = 0.0147), and discontinuations< sup >1</sup >. As the majority of patients diagnosed with mRCC in the US are >65 years, with the largest recent increase in incidence among those ≥75, and front-line treatment now standardly includes immunotherapy (IO), tolerability of new therapies for relapsed or refractory (R/R) mRCC must be acceptable in the elderly and/or IO pretreated populationMethodsData was analyzed to identify relationships between tolerability and advanced age or IO pretreatment. In addition to measures of drug exposure, any grade ≥3 treatment related adverse events (TRAEs) and VEFGR TKI class effect grade ≥3 TRAEs are reported by age (<65, 65–74, ≥75) and prior IO (yes, no)ResultsOf the 343 patients treated on study, 120 (35%) were between age 65 and 75 and 34 (10%) were over 75. Patients received 1.5-2x more cycles of TIVO compared to SOR and fewer overall grade ≥3 TRAEs in all age groups and irrespective of prior IO. Differences in VEGFR TKI class effect TRAEs seen in the total population were retained across most subgroups (table 1). Among patients 75 and over, there were almost half the rate of the dose reductions or discontinuations with TIVO compared to SOR. Prior IO was associated with less asthenia overall, more HTN with TIVO, and more rash but less diarrhea with SORAbstract 349 Table 1Drug exposure, dose modifications, and TRAEs in TIVO-3 by age and prior IOConclusionsTolerability benefits with TIVO compared to SOR in mRCC are retained in elderly patients and those previously treated with IO. This finding, paired with consistently improved PFS in these subpopulations (age >65: HR 0.59, prior IO: HR 0.55), suggests TIVO is a safe and effective option in the context of the current R/R mRCC treatment paradigmTrial RegistrationClinicalTrialsgov Identifier: NCT02627963ReferenceRini B, Pal S, Escudier B, Atkins M, Hutson T, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol 2020;21:95–104Ethics ApprovalThis trial was approved by the institutional review board or ethics committee at every centre and complied with Good Clinical Practice guidelines, the Declaration of Helsinki, and local laws. All patients provided written informed consent before any trial procedure. The trial protocol including the relevant centres is provided in the appendix of the reference 1

Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15615-e15615
Author(s):  
Ugo De Giorgi ◽  
Karim Rihawi ◽  
Michele Aieta ◽  
Giovanni Lo Re ◽  
Teodoro Sava ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Elderly Patients ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Metastatic Renal Cell Cancer ◽  
Grade 3

e15615 Background: Lymphopenia is associated with toxicity and outcome in several cancer types. We assessed the association of pre-treatment lymphopenia with toxicity and clinical outcome of elderly patients with metastatic renal cell cancer treated with first-line sunitinib. We evaluated the prognostic factors in these patients. Methods: We reviewed the clinical files of 181 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1,000/µL. Results: Twenty–nine patients (16.0%) had a baseline lymphocyte counts <1,000/µL, and 152 (84%) ≥1,000/µL. No difference between the two groups was reported in overall response rate (p = 0.207), dose reductions (p = 0.740); discontinuations due to adverse events (p = 0.175), overall incidence of grade 3-4 toxicities (p = 0.112) even if more patients in the group with lymphopenia had grade 3-4 neutropenia (p = 0.017), grade 3-4 thrombocytopenia (p = 0.017) and grade 3-4 diarrhea (p = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (p = 0.015 and p = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (p = 0.007, p < 0.0001 and p = 0.023, respectively). Conclusions: Sunitinib appeared safe and active in elderly patients with lymphopenia. Lymphocyte counts is an independent prognostic factor for OS in elderly patients with mRCC treated with first-line sunitinib.

Survival among older patients with previously treated multiple myeloma treated with selinexor, bortezomib, and dexamethasone (XVd) in the BOSTON study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8019-8019
Author(s):  
Thierry Facon ◽  
Holger W. Auner ◽  
Maria Gavriatopoulou ◽  
Sosana Delimpasi ◽  
Maryana Simonova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lower Incidence ◽  
Treatment Options ◽  
Age Groups ◽  
Progression Free Survival ◽  
Open Label ◽  
Treatment Regimens ◽  
Boston Study ◽  
Grade 3 ◽  
Dose Modifications

8019 Background: Multiple myeloma (MM) typically affects older populations, which are more vulnerable to toxicity with anti-MM treatments. These patients (pts) have significant morbidity and mortality, resulting in a need for dose modifications or alternative suboptimal treatment options. Significant improvements were observed in the BOSTON study with XVd vs Vd in median progression-free survival (PFS), overall response rate (ORR), and rates of peripheral neuropathy (PN); median overall survival (OS) trended in favor of XVd. Methods: The phase 3 randomized BOSTON trial (NCT03110562) is a controlled, open-label study of once weekly XVd vs. twice weekly standard Vd in pts with MM and 1-3 prior treatment regimens. We performed post-hoc analyses to compare survival benefits in pts ≥65 vs < 65 years of age. Results: The BOSTON study enrolled a total of 402 pts between June 2017 and February 2019 that were randomized into XVd or Vd arms. The numbers of pts treated with XVd or Vd who were ≥65 were 109/132 and 86/75 who were < 65, respectively. Baseline characteristics were similar by age although pts ≥65 years were less likely to have received ASCT than those < 65 years (48.4% vs. 25.3%). Median PFS was prolonged with XVd compared with Vd, across both age groups: ≥65 (HR, 0.55 [95% CI, 0.37-0.83] P = 0.002) and < 65, (HR, 0. 74 [95% CI, 0.49-1.11], P = 0.07). Vd was associated with a lower ORR (64.4%) than treatment with XVd (76.1%) (OR, 1.77 [95% CI, 1.00-3.11], P = 0.024) in pts ≥65, while the ORR in those < 65 was 76.7% with XVd and 58.7% (OR, 2.33 [95% CI, 1.18-4.59], P = 0.007) with Vd. As of Jan 2021, the median OS for the overall population was not reached for both arms (HR = 0.86; p = 0.193), with 61 and 75 deaths in the XVd and Vd arms, respectively. Median OS was not reached in pts ≥65 with XVd and was 28.6 months with Vd (HR = 0.60; 95% CI, 0.38-0.94; p = 0.012), while there was no difference in the OS for pts < 65 (HR = 1.52; 95% CI, 0.86-2.68; p = 0.926). Pts ≥65 had a lower incidence of death with XVd as compared to Vd (29 vs 56) and there were 32 deaths with XVd and 19 with Vd in pts < 65. Grade ≥3 treatment-emergent adverse events were not observed more often in older compared to younger pts. Amongst pts ≥65, PN of any grade was lower with XVd (32.1%) compared to Vd (46.5%); (OR 0.57 [95% CI 0.34-0.97], p = 0.017), including a lower incidence of grade ≥3 PN (XVd 4.6% vs. Vd 11.6%). Pts < 65 followed a similar trend of PN AEs of any grade: XVd, 32.6%; Vd, 48.0% (OR 0.42 [95% CI 0.21-0.82], p = 0.006). Conclusions: In an older patient population with a poor prognosis, XVd was associated with a significant survival benefit, improved PFS and OR with reduced PN, and requires relatively short and infrequent clinic visits. XVd may be a simple, effective regimen for pts ≥65 years of age. Clinical trial information: NCT03110562.

Outcomes based on age in the phase 3 METEOR trial of cabozantinib (cabo) vs everolimus (eve) in patients with advanced renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4578-4578 ◽  
Author(s):  
Frede Donskov ◽  
Robert J. Motzer ◽  
Eric Voog ◽  
Elizabeth J. Hovey ◽  
Carsten Grüllich ◽  
...  
Keyword(s):  
Adverse Events ◽  
Older Patients ◽  
Objective Response ◽  
Age Groups ◽  
Progression Free Survival ◽  
Phase 3 ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Dose Reductions

4578 Background: The incidence of RCC increases with age with the highest incidence at ~75 years of age (Znaor, Eur Urol 2015). The Phase 3 METEOR trial (NCT01865747) showed a significant improvement in progression-free survival (PFS; HR 0.58, 95% CI 0.45–0.74; P < 0.0001), overall survival (OS; HR 0.66, 95% CI 0.53–0.83, P = 0.0003), and objective response rate (ORR; 17% vs 3%; P < 0.0001) for cabo compared with eve in patients with advanced RCC previously treated with VEGFR TKIs (Choueiri, NEJM 2015, Lancet Oncol 2016). Here we present outcomes by 3 categories of age for the METEOR trial. Methods: 658 patients were randomized 1:1 to cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Endpoints included PFS, OS, and ORR. Subgroup analyses by age ( < 65, 65 to 74, and ≥75 years) are presented. Results: At baseline, 60% of patients were < 65 years old, 31% were 65 to 74 years old, and 10% were ≥75 years old. Subgroups by age generally had similar baseline characteristics in both arms. The HRs for PFS favored cabo for all age groups (HR 0.53, 95% CI 0.41–0.68 for < 65 years old; 0.53, 95% CI 0.37–0.77 for 65 to 74 years old; and 0.38, 95% CI 0.18–0.79 for ≥75 years old). ORR per independent radiology committee for cabo vs eve was 15% vs 5% for < 65 years old, 21% vs 2% for 65 to 74 years old, and 19% vs 0% for ≥75 years old. HRs for OS also favored cabo (HR 0.72, 95% CI 0.54–0.95 for < 65 years old; 0.66, 95% CI 0.44–0.99 for 65 to 74 years old; and 0.57, 95% CI 0.28–1.14 for ≥75 years old). Median OS for cabo vs eve was 21.4 mo vs 17.1 mo for < 65 years old, not reached vs 18.0 mo for 65 to 74 years old, and 18.4 mo vs 14.0 mo for ≥75 years old. Older patients more frequently had dose reductions (60% with cabo and 22% with eve for < 65 years old vs 85% with cabo and 36% with eve for ≥75 years old). Grade 3 or 4 adverse events were generally consistent with the safety profiles in the overall population although some events such as fatigue and hypertension occurred at a higher rate in older patients. Conclusions: Treatment with cabo improved PFS, ORR, and OS compared with eve in patients with advanced RCC irrespective of age. Adverse events in older patients were more frequently managed with dose reductions. Clinical trial information: NCT01865747.

Effects of pazopanib (PAZ) and sunitinib (SUN) dose modification on safety and efficacy in patients with metastatic renal cell carcinoma (mRCC) from COMPARZ.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4574-4574 ◽  
Author(s):  
Georg A. Bjarnason ◽  
Christian K. Kollmannsberger ◽  
Qasim Ahmad ◽  
Luca Dezzani ◽  
Mohamed Elmeliegy ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Drug Exposure ◽  
Progression Free Survival ◽  
Comparable Efficacy ◽  
Therapeutic Drug ◽  
Open Label ◽  
Safety And Efficacy ◽  
Dose Modification ◽  
Dose Modifications ◽  
Dose Reductions

4574 Background: COMPARZ was a randomized, controlled, open-label, phase 3 trial that demonstrated comparable efficacy of first-line PAZ and SUN, but favorable safety and quality of life profiles for PAZ in patients (pts) with mRCC (NEJM 2013;369:722). We evaluated the relationship between dosing, safety, and efficacy in PAZ- and SUN-treated pts who did or did not undergo dose reduction or interruption resulting from adverse events (AEs) and other reasons. Methods: The AEs and median progression-free survival (mPFS) of PAZ and SUN were evaluated for pts with no, any, 1, and ≥2 dose reductions or dose interruptions lasting ≥7 days. Results: Similar percentages of pts in the PAZ and SUN groups had a dose interruption (44% vs 49%, respectively) or reduction (44% and 51%, respectively). The incidence of AEs in pts from the PAZ and SUN groups with dose modifications was higher compared to those with no dose modifications. Longer mPFS was observed in pts with dose modification (Table). Pts treated with PAZ or SUN with no dose reductions had mPFS of 7.3 months (mos) and 5.5 mos, respectively, whereas pts with any dose reduction had mPFS of 12.5 mos and 13.8 mos, respectively. Similarly, pts treated with PAZ or SUN with no dose interruptions lasting ≥7 days had mPFS of 8.2 mos and 5.6 mos, respectively, whereas those with any dose interruption lasting ≥7 days had mPFS of 12.6 mos and 13.8 mos, respectively. Pts with 2 or more dose interruptions or reductions had mPFS > 16 mos with both SUN and PAZ. Conclusions: Consistent with previous data for SUN, the current analyses showed longer mPFS with PAZ and SUN when dose modification is required to manage toxicity, suggesting that pts are not disadvantaged by such dose reductions or interruptions. Pts not requiring dose modification may have sub-optimal therapeutic drug exposure. Clinical trial information: NCT00720941. [Table: see text]

Lymphopenia and clinical significance associated with tyrosine kinase inhibitors in metastatic renal cell cancer in Guatemalan cohort.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16117-e16117
Author(s):  
Rixci Ramirez ◽  
Daniel Estuardo Rosales Lopez ◽  
Francisco Godinez Jerez ◽  
Alfredo Mansilla ◽  
Carolina Camey ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Cell Cancer ◽  
Age Groups ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival

e16117 Background: Lymphopenia is associated with toxicity and clinical outcomes in several types of cancer. Decrease in absolute lymphocyte count (ALC) has been observed in the treatment with sunitinib. Objective: characterize lymphopenia ( < 1000/µL) associated with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma (mRCC) and its relation to progression free survival (PFS). Methods: A retrospective review of the charts was performed in patients with sunitinib and/or sorafenib between April 2000 and May 2017 in Guatemalan Social Security Institute (IGSS). The Kaplan-Meier models, the Cox regression and the log-rank test are within the groups for progression-free survival. Results: Eighty-nine patients were analyzed, 56 men and 33 women. The age groups < 50 from 51 to 75 and > 75 being these 19, 34 and 34 respectively. Regarding treatment received 56 patients received sunitinib and 47 sorafenib. Lymphopenia was found in 55% and 8% of the treated with sunitinib and sorafenib, respectively (p < 0.001). Focusing on patients treated with sunitinib for all subsequent analyzes, the median PFS was 11 months (95% CI, 6-19). The median PFS was 21 months (95% CI, 11-25) for patients who will not develop lymphopenia compared to 4 months (95% CI, 3-8) in patients with lymphopenia (p = 0, 0001). Conclusions: Lymphopenia related to sunitinib is associated with a decrease in PFS in mRCC. The decrease in lymphocytes can be used as a prognostic biomarker for patients treated with sunitinib in this context. [Table: see text]

Camrelizumab plus famitinib malate in patients with advanced renal cell cancer and unresectable urothelial carcinoma: A multicenter, open-label, single-arm, phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5085-5085
Author(s):  
Yuan-Yuan Qu ◽  
Hongqian Guo ◽  
Hong Luo ◽  
Qing Zou ◽  
Ninazeng Xing ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Antitumour Activity ◽  
Cell Cancer ◽  
Objective Response ◽  
Open Label ◽  
Genitourinary Cancers ◽  
Grade 3

5085 Background: Camrelizumab (SHR-1210) is a humanised anti-PD-1 antibody. Famitinib malate is a tyrosine kinase inhibitor (TKI) against VEGFR-2, PDGFR, c-kit, and FGFR. This is an ongoing, open label, multi-center Phase II study to assess the preliminary efficacy and safety of camrelizumab in combination with famitinib malate in patients (pts) with genitourinary cancers and gynecologic cancers. Here we just report genitourinary cancers results. Methods: Eligible pts were aged 18 or older, who had advanced clear-cell renal-cell carcinoma with their primary tumour resected or unresectable urothelial carcinoma, had an ECOG performance status of 0-1and measurable disease. Previous system treatments were allowed (excluding prior PD-1/PD-L1 inhibitors or famitinib treatment). Famitinib 20 mg was administered orally once daily with SHR-1210 200 mg given intravenously every 3 weeks. We assessed antitumour activity and safety in all pts who received at least one dose treatment. The primary end point was objective response rate (ORR) per RECIST v1.1. Results: From 23 Jan 2019 to 24 Jun2019, 35 pts were enrolled (25 with RCC, 10 with UC). Median previous treatment line was 1 (range, 1-4), and 50.0% of pts had received ≥2 prior therapies in RCC, all pts received one or more-line therapies in UC. At the data cut-off date (Dec 31, 2019), after at least 6 months follow-up, 22 (63%) pts were still receiving study treatment. The most common reason for discontinuing treatments was disease progression (n = 10). 16 pts achieved a confirmed response, all were partial response, with 8 additional > 24 weeks stable disease. the ORR was 52.0% (13/25, 95% CI 31.3% to 72.2%) in RCC and 30.0% (3/10) in UC, the disease control rate was 84.0% (21/25) in RCC and 70.0% in UC. 13/16 confirmed PR pts were still on treatment, the median duration of response is not reached. The most common grade 3-4 treatment-related AEs (TRAEs) were hypertension (17.1%), proteinuria (11.4%), platelet count decreased (8.6%), hand-foot syndrome (8.6%) and anemia (5.7%). Immune-related adverse events were observed in 7 pts (20%) of 35 pts, 1 pt (2.9%) with grade 3 enteritis. Conclusions: The camrelizumab with famitinib combination appeared to show encouraging activity in pts with heavy-treated RCC and UC, and the safety profile of the combination seemed to be manageable and consistent with that of each drug alone. This combination represented a novel potential treatment option for these settings and warranted further investigation. Clinical trial information: NCT03827837 .

The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Safety and efficacy in patients (pts) with non-clear cell (NCC) renal cell carcinoma (RCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5036-5036 ◽  
Author(s):  
W. M. Stadler ◽  
R. A. Figlin ◽  
M. S. Ernstoff ◽  
B. Curti ◽  
K. Pendergrass ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Severe Renal Impairment ◽  
Collecting Duct ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Grade 3

5036 Background: A phase III trial showed that sorafenib (SOR) doubled progression-free survival (PFS) in previously treated pts with clear cell RCC. Activity of SOR in pts with NCC RCC has not been previously reported. Methods: Pts eligible for this open-label, nonrandomized trial in North America were not eligible for other SOR clinical trials, had recovered from prior treatment-related toxicity, and had advanced RCC; ECOG PS of 0–2; age =15 yrs; no treatment with other investigational drugs within 4 wks; life expectancy >2 mos; no active coronary artery disease, ischemia or hypertension; and no severe renal impairment requiring dialysis. In the US, ARCCS enrollment ended with SOR approval in 12/05, and pts were transitioned to commercial drug with NCC pts being eligible for an additional 6-mo follow-up in an extension protocol (EP), which was designed to better assess PFS in NCC. Tumor assessments and radiological evaluations were conducted every 4 wks in the main protocol and every 8 wks in the EP. Results: Of 2,488 pts valid for safety in ARCCS, 212 (8.5%) had NCC RCC classified as papillary, chromophobe, collecting duct, or oncocytoma, of whom 24 enrolled in the EP. Baseline characteristics and efficacy are shown in the table . Grade 3 and 4 adverse events (AEs) with > 2% incidence across all histologies included fatigue 7.1%, hand-foot skin reaction 6.6%, rash/ desquamation 6.2%, hypertension 4.7%, abdominal pain 3.8% dyspnea 3.8%, pleural effusion 3.3%, nausea 3.8%, vomiting 2.4%, and ascites 2.4%. Grade 3 and 4 serious AEs were reported in 20% of patients. Of those enrolled in the EP with NCC, median PFS was 34.5 wks (65.2% censored). Conclusions: SOR was well tolerated among pts with NCC RCC. Within the limitations of no central pathologic review, SOR toxicity in NCC RCC was similar to that in the broader ARCCS population and SOR may have antitumor activity in papillary and chromophobe subtypes. [Table: see text] [Table: see text]

A randomized, open-label, phase II study of afatinib versus cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Analysis of stage 2 (S2) following crossover.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6001-6001 ◽  
Author(s):  
Didier Cupissol ◽  
Tanguy Y. Seiwert ◽  
Jérôme Fayette ◽  
Eva Ehrnrooth ◽  
Alice Sarah Blackman ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Cross Resistance ◽  
Open Label ◽  
Open Label Phase ◽  
Grade 3 ◽  
Stage 1 ◽  
Dose Reductions

6001 Background: This open-label trial assessed the efficacy of the irreversible ErbB Family Blocker afatinib (A) vs cetuximab (C) in R/M HNSCC pts following failure of platinum-containing therapy. In Stage 1 (S1), A and C had confirmed objective response rates (RECIST 1.0) of 16.1% vs 6.5% by investigator review (8.1% vs 9.7% independent central review [ICR]; Seiwert TY, et al. MHNCS 2012. Abs 235). S2 data after crossover are presented. Methods: In S1, pts were randomized 1:1 to oral A 50 mg/day or IV C 250 mg/m2/wk (400 mg/m2 IV loading dose) until progressive disease (PD) or intolerable drug-related adverse events (DRAEs). Pts could then crossover to the other treatment arm (S2), with treatment given until further PD or intolerable DRAEs. Tumor response in S2 (RECIST 1.0) was evaluated at 4 wks after crossover and every 8 wks thereafter. Results: 56% of pts crossed over into S2: 32 from A to C and 36 from C to A. Of these, 88% crossed over after PD and 12% after intolerable DRAEs. Baseline characteristics of S2 pts were similar in the A and C groups and treatment duration in S1 prior to crossover was comparable (A: 3.7 [0.2–15.7] months; C: 3.5 [0.0–12.5] months). Median treatment duration in S2 was 2.1 (0.0–7.6) months for A and 1.2 (0.0–9.9) months for C. Tumor size decreases of ≥30% were observed in 1 pt in each treatment group (ICR). The disease control rate (DCR) for A was 33% vs 19% for C and the median progression-free survival time was 9.3 wks for A and 5.7 wks for C (ICR). The most frequently reported DRAEs (≥20%) for A were rash/acne (56%), diarrhea (53%) and stomatitis (22%), and for C was rash/acne (44%). DRAEs of ≥Grade 3 were seen in 47% of pts treated with A and 16% of pts treated with C. 12 A-treated patients had dose reductions to 40 mg and 1 pt had a further dose reduction to 30 mg; no C-treated pts had dose reductions. Conclusions: R/M HNSCC pts seem to benefit from sequential therapy with A/C or C/A, especially when using A treatment after C failure. Cross resistance is not universally present and further investigation of sequential treatment is warranted. Clinical trial information: NCT00514943.

Phase II trial of palbociclib in recurrent RB-positive anaplastic oligodendroglioma: A Spanish group for research in neurooncology (GEINO) trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2038-2038
Author(s):  
Juan Manuel Sepulveda-Sanchez ◽  
Miguel J. Gil Gil ◽  
Miriam Alonso ◽  
María Ángeles Vaz Salgado ◽  
Elena Vicente ◽  
...  
Keyword(s):  
Phase Ii ◽  
Drug Exposure ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Homozygous Deletion ◽  
Primary Objective ◽  
Cell Cycle Checkpoint ◽  
Open Label ◽  
Number Of Patients ◽  
Grade 3

2038 Background: The pRB-dependent cell cycle checkpoint is altered in the vast majority of anaplastic oligodendrogliomas (AO), either by homozygous deletion or by hypermethylation of CDKN2A and/or CDKN2B, or by amplification and/or overexpression of CDK4. Palbociclib is an oral inhibitor of CDK4 and 6 that has already been shown to be highly active in breast cancer. Methods: We conducted a multicenter, open-label, phase II trial evaluating efficacy and safety of Palbociclib in patients with AO that progressed to radiotherapy and more than one chemotherapy regimen containing Temozolomide and/or Lomustine. Inclusion criteria included: histologically and molecularly confirmed grade III oligodendroglioma (WHO 2016 classification, IDH1/2 mutation and 1p/19 codeletion were mandatory), recurrence after radiotherapy and 1 or 2 chemotherapy regimens and conserved RB protein expression by immunohistochemistry (IHC). Patients were treated with Palbociclib 125 mg/daily 3 weeks on/1off. The primary objective of the study was progression-free survival at 6 months (6M-PFS). Results: Between October 2015 and September 2018, 34 patients were enrolled across ten hospitals. The study was stopped early secondary to lack of efficacy, with 74% of evaluable patients progressing within 6 months. Number of patients alive and free from progression at 6 months after the enrollment was 9 (26%) out of the first 34 patients, below the minimum number required (18 out of 40) to consider Palbociclib as an active drug in this population. With a median follow-up of 11.2 months, the median PFS was 3 months (95% CI: 2.5-3.5 months). Median overall survival (OS) was 23.1 months (95% CI: 17.2-25 months). There were no partial or complete responses and only 11 patients (32%) achieved stable disease as best response. Palbociclib was well tolerated with neutropenia (Grade 3 or 4: 40%) and thrombocytopenia (Grade 3 or 4: 15%) as the most common adverse effects (AEs). Both AEs had no significant impact since there were no episodes of febrile neutropenia or bleeding. Conclusions: Despite the good tolerance and drug exposure, Palbociclib monotherapy did not show favorable activity in recurrent AO. Clinical trial information: NCT02530320.

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