A cohort compassionate-use program with cabazitaxel plus prednisone for patients with metastatic castration-resistant prostate cancer: Interim results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15112-e15112
Author(s):  
Sevil E. Bavbek ◽  
Zafar I Malik ◽  
Giuseppe Di Lorenzo ◽  
Hans-Jorg Scholz ◽  
Inge M van Oort ◽  
...  
Keyword(s):  
Disease Progression ◽  
Safety Data ◽  
Dose Intensity ◽  
Castration Resistant Prostate Cancer ◽  
Compassionate Use ◽  
Regional Lymph Nodes ◽  
Prior Therapy ◽  
Neutropenic Sepsis ◽  
Metastatic Sites ◽  
Ecog Ps

e15112 Background: In the TROPIC trial (NCT00417079), treatment with CbzP produced a statistically significant improvement in overall survival vs mitoxantrone + prednisone (MP) in patients (pts) with mCRPC previously treated with a docetaxel (D)-containing regimen (HR 0.70; p< 0.0001). These results supported the establishment of 2 programs (based on local regulations): a compassionate use (CUP) and an early access program (EAP; NCT01254279). Methods: The aims of the CUP/EAP are to provide drug to pts with mCRPC who may benefit from CbzP prior to commercial availability and further assess CbzP safety profile. Total enrollment for both programs is estimated at 1600 pts from 250 centers globally. Eligible pts receive CbzP (25 mg/m2 Q3W + prednisone 10 mg PO QD) until disease progression, death, unacceptable toxicity or physician/pt decision. Results: Baseline characteristics and safety data are available for the first 399 pts: median age was 68 yrs (range 43–89), with 90.2% ECOG PS 0–1. The median cumulative dose of prior D was 675 mg/m2; prior therapy with MP was permitted. For pts whose disease progressed following D, median time from last dose of D to progression was 4 months; 53.3% of pts experienced disease progression either during or < 3 months after D. 61% of pts had ≥ 2 metastatic sites; the most common were bone (93.2%) and regional lymph nodes (34.4%). At the time of analysis, a median of 4 cycles of CbzP had been administered; 4 pts received ≥ 10 cycles. Median relative dose intensity was 99.2% (range 80.1–104.9). G-CSF was administered to 34.3% of pts in Cycle 1 (6.3% therapeutic, 26.6% prophylactic). Overall, 71.4% of pts had adverse events (AEs; all grades). Most common grade 3-4 AEs were neutropenia 11.3%, febrile neutropenia 6.3%, anemia 2.8%, fatigue 2%, neutropenic sepsis 1.8%, vomiting 1.3% and diarrhea 1%. Eight (2%) treatment-related deaths were reported. Conclusions: The CUP/EAP provides additional safety data for CbzP in a routine clinical practice pt population with heavily pre-treated mCRPC. Treatment with CbzP was tolerable, with a predictable and manageable toxicity profile consistent with data reported for TROPIC and the product labeling.

A cohort compassionate-use program with cabazitaxel plus prednisone for patients with metastatic castration-resistant prostate cancer: Interim results.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 172-172
Author(s):  
Sevil E. Bavbek ◽  
Zafar Malik ◽  
Giuseppe Di Lorenzo ◽  
Hans-Jorg Scholz ◽  
Inge M van Oort ◽  
...  
Keyword(s):  
Disease Progression ◽  
Oral Prednisone ◽  
Safety Data ◽  
Dose Intensity ◽  
Study Drug ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Compassionate Use ◽  
Regional Lymph Nodes ◽  
Neutropenic Sepsis

172 Background: In the Phase III TROPIC trial ( NCT00417079 ), cabazitaxel/prednisone (CbzP) improved overall survival compared with mitoxantrone/prednisone in patients (pts) with mCRPC who had progressed on or after prior docetaxel (D) (HR 0.70; P < 0.0001). The survival benefit observed supported the establishment of 2 programs (based on local regulations): a compassionate use (CUP) and an early access program (EAP) ( NCT01254279 ). Methods: The aims of both programs are to provide drug to pts with mCRPC who may benefit from CbzP prior to commercial availability, and further evaluate CbzP safety profile. Total enrollment for both programs is targeted to be 1,600 pts from 250 centers in Europe, Asia, Latin America and Canada. Eligible pts will receive CbzP (25 mg/m2 Q3W plus oral prednisone 10 mg daily) until disease progression, death, unacceptable toxicity or physician/pt decision. Results: Baseline characteristics and safety data are available for the first 399 pts. Median age was 68 yrs (range 43–89); 90.2% were ECOG PS 0–1. Median cumulative dose of prior D was 675 mg/m2 (median 9 cycles). For pts whose disease progressed following D, the median time from last dose of D to progression was 4 months; 53.3% of pts experienced disease progression either during or < 3 months after D. 61% of pts had ≥ 2 metastatic sites; the most common were bone (93.2%) and regional lymph nodes (34.4%). A median of 4 cycles of CbzP was administered and 4 pts received ≥ 10 cycles. Median relative dose intensity was 99.2% (range 80.1–104.9). G-CSF was administered to 34.3% of pts in Cycle 1 (6.3% therapeutic, 26.6% prophylactic). Overall, 71.4% of pts experienced adverse events (AEs) (all grades) considered related to study drug. The most common Grade 3–4 AEs included neutropenia 11.3%, febrile neutropenia 6.3%, anemia 2.8%, fatigue 2%, neutropenic sepsis 1.8%, vomiting 1.3% and diarrhea 1%. 8 (2%) treatment-related deaths were reported. Conclusions: The CUP/EAP programs provide additional safety data for CbzP in a routine clinical practice population of pts with mCRPC. Treatment with CbzP was tolerable, with a manageable toxicity profile consistent with the data reported for the TROPIC trial.

Preliminary safety results of an Italian early-access program (EAP) with cabazitaxel plus prednisone (CbzP) in patients with docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
Sergio Bracarda ◽  
Giuseppe Di Lorenzo ◽  
Donatello Gasparro ◽  
Paolo Marchetti ◽  
Francesco Boccardo ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Safety Data ◽  
Castration Resistant Prostate Cancer ◽  
Early Access ◽  
Italian Experience ◽  
Grade 3 ◽  
Overall Survival Benefit ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Access Program

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of > 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. Methods: We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m2 Q3W) plus P(10mg bid). Results: Pts were median age 73.5 years (>75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D dose to inclusion was 7.1 months. Overall, 62.5% (10 Pts) had 2 or more metastatic sites (bone 94%, regional/distant lymph nodes 25% and 44%, lung 12.5%, other sites 19%). A limited number of relevant adverse events (AE) were observed. All grade AEs were seen in 14/16 pts (81.3%), with 4/16 pts experiencing grade 3/4 leukopenia, 8/16 pts grade 3 - 4 neutropenia, one patient with febrile neutropenia and one with hypertransaminasaemia. Grade 1-2 asthenia and fatigue were experienced respectively by 2 pts. No grade 3 / 4 diarrhea, vomiting or constipation were observed and no AEs results in death. All pts received at least 2 cycles of CbzP (2÷5) and only one patient permanently discontinued treatment (disease progression). Conclusions: This preliminary analysis of Italian pts enrolled in the EAP provides real world safety data and suggests a good safety profile of cabazitaxel even in heavily pretreated pts, which is in agreement with Italian experience in TROPIC. Results of the entire Italian cohort with a longer follow-up will be presented.

Interim safety analysis of a compassionate-use program (CUP) and early-access program (EAP) providing cabazitaxel (Cbz) plus prednisone (P) to patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5055-5055 ◽  
Author(s):  
Zafar I. Malik ◽  
Giuseppe Di Lorenzo ◽  
Mert Basaran ◽  
Alexandros Ardavanis ◽  
Phillip Parente ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Safety Data ◽  
Real Life ◽  
Dose Intensity ◽  
Median Number ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Metastatic Sites

5055 Background: Cbz + P provides a significant survival benefit vs mitoxantrone + P in pts with mCRPC (Phase III TROPIC study [NCT00417079]; hazard ratio 0.70; p < 0.0001). These findings supported the initiation of ongoing Sanofi-funded CUP and EAP (NCT01254279) to provide access to Cbz prior to commercialization and to collect real-life safety data. Methods: Expected enrollment is ~1600 pts with mCRPC from 250 centers worldwide. Pts receive Cbz (25 mg/m2 Q3W) + P (10 mg oral QD) until progressive disease (PD), death, unacceptable toxicity, physician/pt decision or Cbz commercial availability. Pts are followed until 30 days after last dose. Granulocyte colony-stimulating factor (G-CSF) use is recommended as per ASCO guidance. Results: Interim baseline and safety data from the first 1301 pts treated in 37 countries are now available. Mean age was 68 yrs (22% were ≥ 75 yrs). All pts had an ECOG performance status ≤ 2. Median time from initial prostate cancer diagnosis was 57.6 months and 60% of pts had ≥ 2 metastatic sites; the most common were bone (91%) and lymph nodes (regional 30%, distant 27%). In total, 17% had PD whilst on docetaxel. The median number of Cbz cycles was 6 (range 1–22); median relative dose intensity was 99%. Overall, 837 pts (64%) received G-CSF (n = 123 curative [C], n = 765 prophylactic [P] and n = 99 [C + P]). Of 1142 pts (88%) who discontinued Cbz + P, the most common reasons were PD (44%), adverse event (AE; 27%), physician decision (13%) and commercial availability of Cbz (7%). Grade 3–4 AEs possibly related to Cbz + P occurred in 43% of pts; the most frequent were clinical neutropenia (18%), febrile neutropenia (FN; 7%) and diarrhea (4%). Of 80 pts (6%) with AEs leading to death, the AE was related to Cbz + P in 39 pts (3%). Conclusions: These results provide valuable data on Cbz + P treatment in routine clinical practice, confirming the safety results of clinical trials and showing that treatment with Cbz + P is associated with a manageable safety profile. The incidence of FN seems slightly lower than in TROPIC, owing to more frequent use of G-CSF prophylaxis in the CUP and EAP. Clinical trial information: NCT01254279.

Serum parathyroid hormone and calcium changes in metastatic castration resistant prostate cancer patients receiving enzalutamide in post-docetaxel setting.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 349-349
Author(s):  
Angela Gernone ◽  
Maria Nicla Pappagallo ◽  
Francesco Silvestris ◽  
Keyword(s):  
Androgen Receptor ◽  
Disease Progression ◽  
Bone Disease ◽  
Nuclear Translocation ◽  
Patient Characteristics ◽  
Vitamin D Supplementation ◽  
Castration Resistant Prostate Cancer ◽  
Prior Therapy ◽  
Serum Pth ◽  
Metastatic Sites

349 Background: Among novel hormonal therapeutic targets for post docetaxel mCRPC, Enzalutamide is an oral androgen-receptor blocker disrupting the androgen-receptor nuclear translocation that significantly increases the OS. In this study we evaluated the potential association of both PTH and Ca levels change in pts with mCRPC after the first Enzalutamide administration. Methods: Between 01 and 05/2015, 20 mCRPC pts relapsed after 2-3 prior lines of therapy (docetaxel, cabazitaxel, abiraterone) have been treated with Enzalutamide that was orally administered at 160 mg/day as continuous dosing. Patient characteristics included: median age 67 years (range 50-84), median baseline PSA 120 ng/ml (range 6-1200), median ECOG P S: 1 (range 0-2), Gleason score ≥ 7. In addition 80% of pts had ≥ 2 metastatic sites. Pretreatment baseline and follow up data including measurement of serum Ca and PTH levels (6.5-36.8 pg/ml), ALP, PSA and QoL parameters were evaluated through all lines of therapy. Pts with bone metastasis received zoledronic acid or denosumab with Ca and vitamin D supplementation. Results: In 18/20 pts with bone disease progression we recorded increased PTH levels and, contrarily, decreased Ca levels after 1 month of Enzalutamide despite vit. D and Ca supplementation. PTH levels remained unchanged after 3 months. In 2/20 pts without bone disease progression PTH ranged normal. All pts reported PSA response ≥ 50%, with improved QoL and are still on treatment since Enzalutamide is well tolerated. We did not find PTH change in bone mCRPC pts treated with prior therapy. Conclusions: Our study showed that increase in PTH levels and reduction in Ca levels and increase in PTH levels after 1 month of Enzalutamide treatment is associated with a dramatic reduction of PSA level. These data support a relationship between PTH and Ca changes in pts treated with Enzalutamide and, thus, their changes level may be adopted in clinical practice as surrogate to reflect the drug activity. No studies have evaluated the variations in serum PTH levels following Enzalutamide treatment and whether these early changes relate to the clinical outcome.

KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
Yung-Jue Bang ◽  
Kei Muro ◽  
Charles S. Fuchs ◽  
Talia Golan ◽  
Ravit Geva ◽  
...  
Keyword(s):  
Disease Progression ◽  
Gastroesophageal Junction ◽  
Safety Data ◽  
Prior Therapy ◽  
Grade 3 ◽  
Ecog Ps ◽  
Secondary Results ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

4012 Background: Preliminary analyses from the global, multicohort, phase 2 KEYNOTE-059 (NCT02335411) study suggested that safety of pembro + 5-FU + cisplatin is manageable as 1L therapy in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (cohort 2). We present efficacy and updated safety data from KEYNOTE-059 cohort 2. Methods: Cohort 2 enrolled pts ≥18 y with HER2 – recurrent or metastatic G/GEJ adenocarcinoma, measurable disease, no prior therapy for metastatic/advanced disease, and ECOG PS 0-1. Pts received pembro 200 mg on day 1 of each 21-day cycle + cisplatin 80 mg/m2 for 6 cycles + 5-FU 800 mg/m2 (or capecitabine 1000 mg/m2 in Japan) Q3W for up to 2 y or until disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). End points were safety and tolerability (primary), ORR (RECIST v1.1, by central review), DOR, PFS, and OS (secondary). Results: Of 25 enrolled pts, 64% were men, 68% were Asian, and 64% had PD-L1+ tumors. Median age was 64 y. At data cutoff (Oct 19, 2016), median duration of follow-up was 12.2 mo (range, 1.8 to 19.6) and 84% of pts had discontinued treatment, mainly owing to clinical or radiologic disease progression (64%). ORR (CR + PR) was 60% (95% CI, 38.7-78.9) in all pts. Overall, 32% of pts had SD (95% CI, 14.9-53.5), 4% had PD (95% CI, 0.1-20.4), and 4% were not evaluable (95% CI, 0.1-20.4). ORR was 68.8% (95% CI, 41.3-89.0) in PD-L1+ pts and 37.5% (95% CI, 8.5-75.5) in PD-L1– pts. Median DOR (range) was 4.6 mo (2.6 to 14.4+) in all pts, 4.6 mo (3.2 to 14.4+) in PD-L1+ pts, and 5.4 mo (2.8 to 8.3+) in PD-L1–pts. Median PFS was 6.6 mo (95% CI, 5.9-10.6); median OS was 13.8 mo (95% CI, 7.3-not estimable). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 76% of pts. TRAEs led to discontinuation in 3 pts (grade 3 stomatitis, grade 2 hypoacusis, and grade 1 creatinine increase). No TRAEs were fatal. Conclusions: Pembro + 5-FU + cisplatin showed manageable safety and encouraging antitumor activity as 1L therapy for pts with advanced G/GEJ cancer. Further exploration of pembro + 5-FU + cisplatin in this setting is warranted. Clinical trial information: NCT02335411.

Docetaxel (T) followed by capecitabine (X) as first-line chemotherapy in patients (pts) with metastatic breast cancer (MBC): Preliminary findings from a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10692-10692
Author(s):  
J. L. Bayo ◽  
M. Lomas ◽  
J. Salvador ◽  
M. Ruiz ◽  
A. Moreno
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
First Line ◽  
Recent Trial ◽  
Highly Active ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Ecog Ps

10692 Background: X and T are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-pretreated MBC [O’Shaughnessy et al. J Clin Oncol 2002]. The aim of this trial was to evaluate the efficacy and safety of sequentially administered T then X as first-line treatment in MBC. Methods: Pts ≥ 18 years with previously untreated, HER2neu-negative MBC, ECOG PS ≤ 2, were included in this prospective, multicenter, non-randomized, phase II study. Pts received 3 cycles of T (100mg/m2 d1) followed by 3 cycles of X (1250mg/m2 bid d1–14), every 3 weeks. Results: To date, 38 pts are evaluable for safety and 33 pts for efficacy. Baseline characteristics: median age 54.4 years (range 33–76); PS ≥ 1 50%; 36 (95%) pts had previous (neo)adjuvant anthracyclines, 8 (21%) concomitant with paclitaxel. The most frequent metastatic sites were: bone 47%, nodes 39% and liver 36%. 69% of pts had ≥ 2 metastatic sites. To date, 38 pts have received 3 cycles of T and 33 have also received 3 cycles of X. A total of 195 cycles have been administered: T 108 cycles (median 3, range 1–3); X 87 cycles (median 3, range 1–3). Dose reductions and interruptions for T vs. X were 32 vs. 21% and 21 vs. 21%, respectively. Median relative dose intensity: T 0.97 (range 0.62–1.00), X 0.93 (range 0.26–1.00). T grade 3/4 toxicities (37 evaluable pts): asthenia 19%, mucositis 16%, nausea 13%, febrile neutropenia 11%, rash 5%, diarrhea 5%, infection 3%. X grade 3/4 toxicities (33 evaluable pts): hand-foot syndrome 9%, diarrhea 9%, vomiting 9%, asthenia 6%, nausea 3%, anorexia 3%. In the 33 pts evaluable for efficacy, the RR was 61%, including 4 CRs and 16 PRs. At a median follow-up of 6.1 months, median TTP has not yet been reached. Conclusions: These preliminary results show that the sequential regimen of T followed by X is feasible, effective and well tolerated in first-line MBC, although giving X before T should also be investigated. Findings from a recent trial of XT vs. T followed by X [Beslija et al. ECCO 2005] suggest that XT should be standard in fit poor-prognosis pts with aggressive disease. No significant financial relationships to disclose.

Efficacy of abiraterone acetate in the treatment of castration-resistant prostate cancer: Early results from the German compassionate-use program.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15195-e15195
Author(s):  
Carsten Henning Ohlmann ◽  
Michael Stöckle ◽  
David A. Pfister ◽  
Axel Heidenreich ◽  
Axel S. Merseburger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Objective Response ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Compassionate Use ◽  
Castration Resistant ◽  
Psa Progression

e15195 Background: Abiraterone acetate (AA) plus prednisone (P) has demonstrated an improved survival of patients with castration-resistant prostate cancer (CRPC) compared to placebo plus P in a large phase III trial. In Germany, patients were able to receive AA within a compassionate-use program (CUP). Here, we report the first results of the program. Methods: Patients were eligible for the CUP if they progressed on or after at least one cytotoxic chemotherapy regimens. For CUP entry, patients were considered to have disease progression if they had radiographic evidence of disease progression in soft tissue or bone with or without PSA-progression and ongoing androgen deprivation. Patients received AA 1000mg daily plus prednisone 5mg BID until progression of disease or unacceptable toxicity. Results: Between 02-05/2011, 398 patients were registered for the CUP in Germany. Data from 191/350 (47.9%) of the patients treated at 10 different sites were available for evaluation of efficacy. Median age was 70.72yrs (52.35-87.61) and patients received a median of 1 (1-4) chemotherapy lines prior to CUP entry. Median PSA at baseline was 220.5 ng/ml (0.47-4245); 168 (88%) of patients presented with bone metastasis. With regard to efficacy, 64/191 (33.5%) of the patients showed an unconfirmed PSA-response ≥50%. At a median follow-up of 5.3 months, 51/191 (26.7%) patients had died, resulting in a median PSA-progression free and overall survival of 8.3 and 10.61 months, respectively. In a subset of patients (71/191, 37.2%) data regarding objective response was available with 25/71 (35.2%) achieving an objective response. Data from 114 pts. revealed fatigue (20.3%), hot flushes (15.8%), edema (10.6%), elevated liver enzymes (8.0%) and asthenia (7.9%) being the most frequent toxicities (any grade). Conclusions: Treatment of CRPC patients with AA outside controlled clinical trials leads to considerable PSA- and objective response rates with a favourable toxicity profile, comparable to the results from COU-AA-301 registration trial. Due to the short median follow-up, conclusions regarding PSA-progression free and overall survival may not be drawn.

Interim safety results of a global early access protocol (EAP) of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) progressing after taxane-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5059-5059
Author(s):  
Daniel J. George ◽  
Tracy McGowan ◽  
Gedske Daugaard ◽  
Thomas W. Flaig ◽  
Lajos Geczi ◽  
...  
Keyword(s):  
Latin America ◽  
Disease Progression ◽  
Controlled Trial ◽  
Safety Data ◽  
Osteoporotic Fractures ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Early Access ◽  
Grade 3

5059 Background: The COU-AA-301 phase 3 trial showed significantly longer overall survival for AA + prednisone (P) than P alone in mCRPC pts refractory to docetaxel. This global EAP was conducted in the same setting to collect additional safety data. Methods: Open-label EAP in pts with mCRPC who progressed after 1 - 2 chemotherapy regimens (≥ 1 taxane), resided in areas where AA was unavailable and were ineligible for ongoing clinical trials of AA. Pts received AA (1000 mg PO/d) plus P (5 mg bid) in 28 d cycles until disease progression. Only serious or clinically important adverse events (AEs) were to be reported by investigators. First interim results (clinical cut-off date: December 31, 2011), reported as part of regulatory submissions, are presented. Results: 1079 pts from 15 countries were included: N. America (47%), Europe (29%), Australia (13%), Latin America (7%), and Asia (3%). Median age: 70 years (range: 47 – 93); 89% of pts were White. Median treatment exposure, incl. pts still on treatment (285 pts), was ≈ 3 months. 620 pts (58%) received ≥ 4 treatment cycles, 58 pts (5%) received ≥ 8 cycles. 441 pts (41%) reported serious or clinically important AEs, which were treatment-related in 154 pts (14%). Most common grade 3-4 AEs: ↑ALP (6%), anemia (3%), hypertension (3%), back pain (2%), and fatigue (2%). Grade 3-4 AEs of special interest were infrequent: LFT abnormalities (8%), hypertension (3%), cardiac disorders (2%), hypokalemia (< 1%), fluid retention/edema (< 1%), osteoporotic fractures (< 1%). Main reason for discontinuation (795 pts): disease progression, in 335 pts (31%). 253 pts (23%) discontinued after marketing authorization. Discontinuations due to treatment-emergent AEs, death, or withdrawal of consent were < 6% each. Conclusions: The safety profile observed in these EAP interim results was consistent with that in the COU-AA-301 randomized, placebo controlled trial conducted in the same clinical setting. No new safety signals with AA plus P were detected in this expanded patient population, which included pts from Latin America and Asia, i.e. regions that did not participate in COU-AA-301. Clinical trial information: NCT01217697.

Phase II trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) for disease progression after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell renal cell carcinoma (mccRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5008-5008 ◽  
Author(s):  
Chung-Han Lee ◽  
Amishi Yogesh Shah ◽  
James J Hsieh ◽  
Arpit Rao ◽  
Alvaro Pinto ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Duration Of Response ◽  
Vegfr Inhibitor

5008 Background: LEN, a multikinase VEGFR inhibitor, plus everolimus is approved for advanced RCC after prior VEGF-targeted therapy. PEMBRO, an anti-PD-1 antibody, plus axitinib is approved as first-line therapy of advanced RCC. We report phase 2 results of the RCC cohort of a phase 1b/2 trial (Study 111/KEYNOTE-146) of LEN + PEMBRO in patients (pts) who progressed after ICI therapy. Methods: We performed a multicenter, open-label study of pts with mccRCC, who previously had disease progression by RECIST (confirmed ≥ 4 weeks later) during or following ICI therapy. Pts had measurable disease by immune-related RECIST, and ≥ 1 prior therapy. Pts received LEN 20 mg orally once daily plus PEMBRO 200 mg IV every 3 weeks until disease progression or toxicity. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks. The primary endpoint was objective response rate (ORR) at Week 24 by irRECIST. Results: 104 pts were enrolled. At data cutoff (January 12, 2020), 71 (69%) pts were still on study treatment. Most pts had ≥2 prior anticancer regimens (58%). 91 of 104 pts were evaluable for response at Week 12 (13 pts NE at Week 12); 46 of 91 pts achieved a confirmed partial response for an ORR of 51% (Table). Median progression-free survival (PFS) was 11.7 months and median duration of response (DOR) was 9.9 months. The most common treatment-related adverse events (TRAEs) were fatigue (49%), diarrhea (44%), proteinuria (37%), hypertension (31%), nausea (31%), dysphonia (29%), stomatitis (29%), and arthralgia (27%). There was 1 grade 5 TRAE (upper gastrointestinal hemorrhage). 43% of pts required dose reduction and 12% of pts discontinued treatment due to TRAEs. Response and safety data will be updated to include all pts evaluable at an April 9, 2020 cut-off. Conclusions: LEN + PEMBRO demonstrated promising antitumor activity in pts with mccRCC with disease progression following ICI therapy. No new safety signals were detected. Efficacy outcomes by investigator review per irRECIST. Clinical trial information: NCT02501096 . [Table: see text]

Fractionated docetaxel and radium-223 (Ra223) in metastatic castration-resistant prostate cancer (CRPC): A phase I trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS175-TPS175
Author(s):  
Brendan James Connell ◽  
Edmund Folefac ◽  
Clara Hwang ◽  
Christian Lawlor ◽  
Paul Mathew
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Objective Response ◽  
Dose Intensity ◽  
Dose Schedule ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Highly Active ◽  
Radium 223 ◽  
Ecog Ps

TPS175 Background: Disease progression following highly-active androgen-axis therapy (HAAT) in CRPC remains bone-dominant and docetaxel-responsive. Combination bone-homing Ra223 isotope therapy with docetaxel would be a logical combination therapy to follow but myelosuppression is dose-limiting. With 3-weekly bolus schedules of docetaxel (D), dose-reduction to 60mg/m2 Q3wkly and Ra223 to every 6 weeks has been required representing a reduction in the dose-intensity of both agents. Fractionated schedules of docetaxel Q2wkly (DQ2) have comparable activity to D 75mg/m2 Q3wkly (DQ3) with mitigated myelosuppression. We hypothesize that a fractionated dose-schedule of DQ2 in combination with standard Ra223 dosing will be feasible without reduction in dose-intensity of Ra-223 or D. Methods: Outcomes: The primary objective is to determine the feasibility and maximal tolerated dose (MTD) of the combination. Secondary objectives include PSA kinetics, objective response, bone marker outcomes, progression free and overall survival, and description of toxicity and quality of life. Eligibility: Progressive bone-metastatic CRPC, ECOG PS 0-2 with no prior Ra223, no prior docetaxel for CRPC, and no bulky visceral disease. Design: Phase I (6+6) design; 4 week lead-in with DQ2. Dose-level 1a: 40mg/m2; 2a: 50mg/m2, both with PEGylated G-CSF on Day 16. If tolerated (≤ Grade 2 toxicity, ANC ≥ 1500, Platelets ≥ 100,000), lead-in is followed by C1D1 of DQ2 plus Ra223 Q4wkly x 6 doses. Dose level 1a has accrued 6 subjects without DLT. Enrollment to Dose Level 2a began in August, 2020. An expansion cohort of 25 subjects is planned after the MTD is determined. Clinical trial information: NCT03737370.

Sign in / Sign up

Export Citation Format

Share Document