Safety and efficacy of AMG 386 in combination with sunitinib in patients with metastatic renal cell carcinoma (mRCC) in an open-label multicenter phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4606-4606 ◽  
Author(s):  
Michael B. Atkins ◽  
Alain Ravaud ◽  
Gwenaelle Gravis ◽  
Kazimierz Drosik ◽  
Tomasz Demkow ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Angiogenesis Inhibitors ◽  
Risk Scores ◽  
Open Label ◽  
Safety And Efficacy ◽  
Kaplan Meier ◽  
Amg 386 ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Modifications

4606 Background: AMG 386, an investigational peptide-Fc fusion protein, inhibits angiogenesis by disrupting the angiopoietin/Tie2 axis. We evaluated the safety and efficacy of AMG 386 plus sunitinib in patients (pts) with mRCC. Methods: Adults with mRCC who were naïve to angiogenesis inhibitors were sequentially enrolled to 2 cohorts: sunitinib 50 mg PO QD (4 wks on, 2 wks off) plus AMG 386 at 10 mg/kg (A) or 15 mg/kg (B) IV QW. Primary endpoints: adverse events (AEs), dose interruptions/reductions due to AEs in the first 12 wks of treatment; secondary endpoints included: progression-free survival (PFS) and response rate (ORR). Results: 85 pts received ≥1 dose of study medication (A/B, n=43/42). In A/B, 88%/76% were male and 30%/36% were age ≥65; MSKCC risk scores were low (40%/36%) or intermediate (60%/62%). For A/B: median follow-up time was 19.6/12.0 mos; AMG 386 discontinuations due to AEs were 16%/29%; and grade ≥3 treatment-related AEs occurred in 72%/74% with virtually all attributed to sunitinib. Grade 3 AEs occurring with >5% frequency were hypertension, hand foot syndrome, asthenia, fatigue, elevated lipase, diarrhea, mucositis, vomiting, thrombocytopenia, and neutropenia, with no distinction between dose levels. The percentage of pts with sunitinib dose interruptions within the first 12 wks (A/B, 58%/57%) met the prespecified criteria. One pt in B had fatal acute pulmonary edema. No pt developed anti-AMG 386 antibodies. The Kaplan-Meier estimate (95% CI) of PFS was 13.9 (10.4, 19.2) mos in A; PFS in B is not yet mature with only 21% of pts having disease progression. ORR (95% CI) was 58% (42, 73) in A including 1 CR, and 59% (42, 74) in B. Conclusions: In pts with mRCC, AMG 386 at 10 and 15 mg/kg combined with sunitinib appeared to be tolerable. Reported sunitinib dose modifications for the observation period were within the prespecified range. Efficacy results suggest potential benefit for the addition of AMG 386 to sunitinib.

Phase II study to evaluate safety and efficacy of MEDI4736 (durvalumab) + radiotherapy in patients with newly diagnosed unmethylated MGMT glioblastoma (new unmeth GBM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2032-2032 ◽  
Author(s):  
David A. Reardon ◽  
Thomas Joseph Kaley ◽  
Jorg Dietrich ◽  
Jennifer Leigh Clarke ◽  
Gavin Dunn ◽  
...  
Keyword(s):  
Tumor Antigens ◽  
Progression Free Survival ◽  
Open Label ◽  
Safety And Efficacy ◽  
Lung Cancers ◽  
Kaplan Meier ◽  
Secondary Endpoints ◽  
Radiation Induced ◽  
Human Igg1 ◽  
Grade 3

2032 Background: Durvalumab (durva), a human IgG1 monoclonal Ab against PD-L1, is FDA-approved for selected patients with bladder and non-small cell lung cancers. PD-L1 is expressed by some GBM tumors, while GBM infiltrating T lymphocytes often express PD-1. Radiation induced cell death releases tumor antigens and could potentiate anti-PD-(L)1 therapy. Methods: This ongoing Phase 2 open-label study (NCT02336165) evaluates the safety and efficacy of durva (10 mg/kg every 2 weeks) in 5 GBM cohorts. Results are presented for Cohort A, which evaluates durva + standard radiotherapy (RT, 60 Gy over 30 fractions) followed by durva monotherapy in patients with new unmeth GBM after maximum safe resection. The primary efficacy endpoint for Cohort A is overall survival at 12 months (OS12); secondary endpoints include safety/tolerability, tumor response rate, and progression-free survival (PFS). Historical benchmarks of median OS and OS12 for patients with new unmeth GBM following standard therapy are 12.7 months and 50%, respectively (EORTC 26981-22981/NCIC CE.3). Results: Median follow-up of 40 enrolled patients is 24.5 months (data cutoff = 05 Nov 2018). Baseline characteristics: male, 70%; median age, 57.0 [22 to 77] years; ECOG PS0, 60.0%; ECOG PS1, 40.0%; measurable disease, 80.0%; and dexamethasone use, 32.5%. Treatment-related adverse events with maximum CTCAE grade ≥ 3 occurred in 14 (35.0%) patients; the most common were asymptomatic increased lipase (n = 6) and increased amylase (n = 2). Twenty-four of 40 patients were alive at 12 months (Kaplan-Meier for OS12, 60.0% [90% CI: 46.1, 71.4]). Median OS was 15.1 (95% CI: 12.0, 18.4) months. As of 05 Nov 2018, 8 (20%) patients remain alive, with ongoing survival ranging from 15.7 to 34.9 months. Tumor immunocorrelative and systemic studies are pending. Conclusions: This is the first study report of anti-PD-L1 for new GBM. Durva was well tolerated when combined with RT and seemed to have efficacy among patients with new unmeth GBM. Further studies may be warranted. Clinical trial information: NCT02336165.

Efficacy and safety of sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC) and lung metastases (mets) only at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15098-e15098
Author(s):  
Nobuo Shinohara ◽  
Hideyuki Akaza ◽  
Yoshihiko Tomita ◽  
Takeshi Yuasa ◽  
Hiroyuki Fujimoto ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Objective Response ◽  
White Blood Cells ◽  
Progression Free Survival ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15098 Background: The lungs may be the sole site of mets in RCC.In this retrospective analysis, we analyzed the efficacy and safety of SU in mRCC pts from a global phase (ph) III study and a Japanese ph II study who had lung mets only at baseline. Methods: In the ph III study, treatment (Tx)-naïve mRCC pts were randomized 1:1 to SU 50 mg/d on a 4-weeks-on-2-weeks-off schedule (n=375) or interferon-a (IFN) 9 MU subcutaneously TIW (n=360). In the single-arm ph II study, Tx-naïve (n=25) and cytokine refractory (n=26) mRCC pts received the same SU Tx. In the ph III study, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, with median values compared by log-rank test. In both studies, objective response rate (ORR) was calculated with a two-sided 95% CI. PFS, OS, ORR, and safety were analyzed at final data cutoff. Results: In the ph III study, 31 (8%) and 42 (11%) pts in the SU and IFN groups, respectively, had lung mets only, compared with 12 (24%) in the ph II study. Baseline characteristics in lung mets pts were similar to all pts. In lung mets pts from the ph III study, ORR was higher with SU than with IFN (58.1% [95% CI: 39.1–75.5] vs. 19.0% [95% CI: 8.6–34.1]; P<0.001); there was a trend for longer median PFS with SU (14.1 vs. 7.8 months; HR: 0.531 [95% CI: 0.278–1.015]; P=0.0513); and median OS was comparable in both Tx subgroups (HR: 0.739 [95% CI: 0.335–1.628]; P=0.4507), although, at 25% of events, median OS was 22.9 months with SU vs. 15.8 months with IFN. In lung mets pts from the ph II study, ORR was 75.0% (95% CI: 42.8–94.5); at the time of analysis, median PFS and OS had not been reached; 4 pts (33%) had died due to any cause and 8 (67%) were alive without disease progression. The most common grade ≥3 SU-related AEs were fatigue, hand-foot syndrome, and diarrhea (all 19%) in the ph III study, and decreased platelets (100%), white blood cells (92%), and neutrophils (92%) in the ph II study. Conclusions: In the ph III study, Tx-naïve mRCC pts with lung mets only had significantly higher ORR and a trend for improved PFS and OS with SU compared with IFN. In the Japanese ph II study, ORR with SU was 75% in lung mets pts. Thus, 1st-line use of SU in mRCC pts with lung mets should be encouraged.

scholarly journals Comparison between the three oxaliplatin-based regimens with bevacizumab in patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 687-687
Author(s):  
Yoshihito Ohhara ◽  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Nobuyuki Mizunuma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Kaplan Meier ◽  
Hand Foot Syndrome ◽  
Chemotherapeutic Treatment ◽  
Grade 3 ◽  
First Line Treatment

687 Background: XELOX (capecitabine/L-OHP) therapy that includes orally administered fluoropyrimidine instead of infusional fluorouracil (5-FU) was approved for metastatic colorectal cancer (mCRC) in Sep 2009 in Japan. A pivotal trial (NO16966 study) demonstrated the non-inferiority of XELOX to FOLFOX (5-FU/L-OHP/LV) and the superiority of those L-OHP-based regimens plus bevacizumab (BV) to those without in the first-line treatment of mCRC. We evaluated the safety and efficacy of XELO+BV compared with FOLFOX4 or mFOLFOX6 plus BV in the first-line treatment for mCRC patients at a single institute. Methods: Between Jun 2007 and Nov 2008, 85 patients received FOLFOX4+BV (FF4 arm), between Dec 2008 and Sep 2009, 40 patients received mFOLFOX6+BV (FF6 arm), and between Oct 2009 and Sep 2010, 60 patients received XELOX+BV (XELOX arm). The best overall responses were evaluated using RECIST 1.0 during chemotherapeutic treatment, and adverse events were graded according to CTCAE ver.3.0. Progression-free survival (PFS) was estimated by Kaplan-Meier methods. Results: Characteristics of patients of FF4 arm, FF6 arm, and XELOX arm were below: median age, 60 yr vs. 62 yr vs. 60.5 yr; gender (male), 48.2 % vs. 62.5 % vs. 58.3%. The overall response rates (CR+PR) were 61.1 %, 72.5 %, and 75 % (95% CI; 50.6-71.8%, 58.0-87.0%, and 63.7-86.3%). Median PFS were 17.0 months, 15.5 months, and 14.4 months, respectively (cut-off: Aug 31, 2011). There were no statistical significances not only between FF4 arm and FF6 arm (log-rank; p=0.641), but also between XELOX arm and FF4+FF6 (FOLFOX) arm (log-rank; p=0.138). FOLFOX arm was associated with higher incidence of grade 3/4 neutropenia than XELOX arm. Grade3 diarrhea and hand-foot syndrome (HFS) were more frequent in XELOX arm. Conclusions: This study suggests that XELOX arm was equal to FOLFOX arm, regardless of regimen, in tumor response and PFS. Further follow-up is necessary to confirm the benefit on survival.

SAVOIR: A phase III study of savolitinib versus sunitinib in pts with MET-driven papillary renal cell carcinoma (PRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Toni K. Choueiri ◽  
Daniel Yick Chin Heng ◽  
Jae-Lyun Lee ◽  
Mathilde Cancel ◽  
Remy B Verheijen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chromosome 7 ◽  
Phase Iii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Modifications

5002 Background: PRCC is the most common type of non-clear cell RCC, accounting for 10–15% of renal malignancies. As a subset of PRCC cases are MET-driven, MET inhibition may be an appropriate targeted treatment approach. In a single-arm Phase II study, savolitinib (AZD6094, HMPL‐504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in pts with MET-driven PRCC (Choueiri et al. JCO 2017). The Phase III SAVOIR study (NCT03091192) further assessed savolitinib vs standard of care sunitinib in pts with MET-driven PRCC. Methods: In this open-label (sponsor blinded), randomized study, pts with centrally confirmed MET-driven ( MET and/or HGF amplification, chromosome 7 gain and/or MET kinase domain mutations), metastatic PRCC were randomized to savolitinib 600 mg once daily (QD), or sunitinib 50 mg QD 4 weeks on / 2 weeks off. Primary objective was progression-free survival (PFS; RECIST 1.1 by blinded independent central review). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety and tolerability. Results: After external data on predicted PFS with sunitinib in pts with MET-driven disease became available, study enrollment was closed. At data cutoff (Aug 2019), only 60 of the planned 180 pts were randomized (savolitinib n = 33; sunitinib n = 27). Most had chromosome 7 gain (savolitinib 91%; sunitinib 96%) and no prior therapy (savolitinib 85%; sunitinib 93%). PFS, OS, and ORR were numerically improved with savolitinib vs sunitinib (Table). CTCAE grade ≥3 adverse events (AEs) were reported in 42% and 81% of pts; dose modifications were related to AEs in 30% and 74% of pts with savolitinib and sunitinib respectively. After discontinuation, 36% of all savolitinib and 19% of all sunitinib pts received subsequent anticancer therapy. Conclusions: Although pt numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy and an improved safety profile vs sunitinib, with fewer grade ≥3 AEs and fewer dose modifications required. Sunitinib performance was poorer than expected based on external retrospective data. Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted. Clinical trial information: NCT03091192 . [Table: see text]

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.

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]

Safety and Efficacy of Pomalidomide Plus Low-Dose Dexamethasone (POM + LoDEX) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) in Italy: A Subanalysis of the Stratus Trial (MM-010)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5376-5376
Author(s):  
Michele Cavo ◽  
Paolo Corradini ◽  
Francesco Di Raimondo ◽  
Mario Petrini ◽  
Anna Maria Cafro ◽  
...  
Keyword(s):  
Research Funding ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
The United States ◽  
High Dose ◽  
Open Label ◽  
Safety And Efficacy ◽  
Overall Response ◽  
Heavily Pretreated ◽  
Grade 3

Abstract Introduction: For pts with RRMM who have failed or progressed on treatment (Tx) with newer agents, such as lenalidomide (LEN) and bortezomib (BORT), there are few Tx options, and overall survival (OS) is short (Kumar et al, Leukemia, 2012). POM is a distinct immunomodulatory agent with tumoricidal and immunoregulatory effects, and POM + LoDEX is approved in the United States and European Union for the Tx of pts with RRMM who have had ≥ 2 prior Tx, including LEN and BORT. Tx with POM + LoDEX has shown statistically greater survival benefits than high-dose DEX (MM-003; San Miguel et al, Lancet Oncol, 2013) or POM alone (MM-002; Richardson et al, Blood, 2014). POM + LoDEX has also demonstrated high overall response rates in pts with RRMM in the STRATUS trial (MM-010), a single-arm, open-label phase 3b study being conducted in 19 countries across Europe with a primary endpoint of safety (Dimopoulos et al, EHA 2015). Italian pts constituted the largest national subset in MM-010; hence, this subanalysis examines the safety and efficacy of POM + LoDEX in pts from Italy. Patients and Methods: Pts with RRMM (progressive disease [PD] on or within 60 days of last prior Tx) who had experienced Tx failure with BORT and LEN and had received adequate prior alkylator therapy were eligible. Pts received POM 4 mg on days 1-21 of a 28-day cycle in combination with DEX 40 mg (20 mg for pts aged > 75 yrs) on days 1, 8, 15, and 22. Thromboprophylaxis was required for all pts, and Tx was continued until PD or unacceptable toxicity. Results: A total of 219 pts were enrolled in MM-010 in Italy. The median age of this patient population was 67.0 yrs (range, 42-84 yrs), and 54.8% of pts were male. The median time since diagnosis was 5.5 yrs, and 37.0% of pts were International Staging System stage III. Patients were heavily pretreated, with a median of 4 prior anti-myeloma regimens (range, 2-11), and most pts were refractory to LEN (95%), BORT (82.2%), or both LEN and BORT (78.1%). As of May 4, 2015, 2 pts (0.9%) were not treated, 54 pts (24.7%) were still on treatment, and 163 pts (74.4%) had discontinued. After a median follow-up of 11.3 mos, in the intention-to-treat population, the overall response rate was 37.9% (range, 31.4%-44.7%), the median duration of response was 6.8 mos (95% CI, 4.9-10.8 mos), progression-free survival (PFS) was 5.2 mos (95% CI, 4.4-6.4 mos), and OS was 12.0 mos (95% CI, 10.6-15.2 mos). The most frequent grade 3/4 treatment-emergent AEs were neutropenia (56.7%), anemia (25.8%), thrombocytopenia (23.5%), and pneumonia (12.4%). Incidence of grade 3/4 venous thromboembolism (deep vein thrombosis and pulmonary embolism) and peripheral neuropathy were infrequent (2.3% and 0%, respectively). The most common reasons for discontinuation were disease progression (49.8%), death (10.0%), and adverse events (AEs; 5.0%). AEs led to dose reductions or interruptions of POM in 23.0% and 71.0% of pts, respectively, and the median relative dose intensity for POM was 0.90. Conclusions: In line with previous studies, POM + LoDEX was active in Italian pts, a representative subset of the heavily pretreated MM-010 population. PFS and OS were consistent with those seen in previous trials. POM + LoDEX treatment was well tolerated, and discontinuations due to AEs were infrequent, consistent with the well-known toxicity profile and the appropriate drug management. This study confirms that POM + LoDEX is effective in patients with advanced RRMM, including those who have experienced failure of prior Tx with BORT and/or LEN. Disclosures Cavo: Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Petrini:Novartis: Research Funding; Celgene Corporation: Research Funding; Italfarmaco: Research Funding; Roche: Research Funding. Caravita di Toritto:Celgene Corporation: Honoraria, Research Funding. Offidani:Celgene, Janssen: Honoraria. Petrucci:Celgene Corporation: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria; Mundipharma: Honoraria; BMS: Honoraria. Rodeghiero:Celgene Corporation: Honoraria, Research Funding. Simcock:Celgene Corporation: Employment. Slaughter:Celgene Corporation: Employment, Equity Ownership. Herring:Celgene Corporation: Employment. Peluso:Celgene Corporation: Employment. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria.

Trastuzumab (T) plus capecitabine (C) in heavily pretreated patients (pts) with advanced breast cancer (ABC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1055-1055
Author(s):  
R. Bartsch ◽  
C. Wenzel ◽  
G. Altorjai ◽  
U. Pluschnig ◽  
G. J. Locker ◽  
...  
Keyword(s):  
Complete Response ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Hand Foot Syndrome ◽  
Heavily Pretreated ◽  
Product Limit ◽  
Grade 3 ◽  
Line Setting ◽  
Dose Modifications

1055 Background: In pts with Her2 positive ABC, taxane or vinorelbine plus T are among the most widely applied options in the first line setting. We evaluated the efficacy and tolerability of TC in pts with Her2 positive ABC after anthracycline and docetaxel or vinorelbine failure. Methods: Forty consecutive pts (median age 57.5 years) were included. As of December 2006, all are evaluable for toxicity and 35 for response. C was administered at a daily dose of 2,500 mg for two consecutive weeks (w) every 3 w, with dose modifications if necessary. T was administered in 3 w cycles at a dose of 6 mg/kg bodyweight after a loading dose of 8 mg/kg. Time to progression (TTP) was defined as primary endpoint. Response was evaluated every three months (m) using UICC criteria. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Differences in TTP for 2nd line and beyond 2nd line were analyzed with the log-rang test. Results: All pts had prior exposure to an anthracycline and at least one anti-microtuble agent (i.e. a taxane or vinorelbine). All had at least one earlier T containing treatment line for ABC. Median time of observation was 18.5 m. We observed a complete response in 2.9%, partial response in 20%, stable disease = 6 months in 48.6%, and progression in 28.6% of pts. OS was median 24 m (95% CI 20.3–27.7), and TTP 8 m (95% CI 5.8–10.1). No significant difference was found for 2nd and beyond 2nd line treatment. Diarrhoea (5%) and hand foot syndrome (16%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. A dose reduction was necessary in 22.5%. Two pts developed brain metastases (BM) while on therapy, 6 had BM at time of treatment initiation, a further 5 developed BM during follow up. Of 6 pts with BM, 3 gained clinical benefit from treatment (one pt not yet evaluable). Conclusions: TC appears to be an effective and safe option as salvage therapy in a heavily pretreated population. TTP and response rates are similar to results from C plus lapatinib. Of note is the activity in pts with BM. Further, only 2 pts (5%) developed BM while on treatment. Therefore, a direct comparison of TC with C plus lapatinib or T plus lapatinib seems warranted. No significant financial relationships to disclose.

A retrospective cohort study evaluating the safety and efficacy of TAS-102 in patients with metastatic colorectal cancer (HGCSG1503): Analysis of cases of prior regorafenib.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 832-832
Author(s):  
Atsushi Ishiguro ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Takuro Saiki ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Safety And Efficacy ◽  
Kaplan Meier ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps ◽  
Initial Starting

832 Background: The J003 trial and RECOURSE trial revealed the safety and efficacy of TAS-102 for patients with metastatic colorectal cancer (mCRC). In March 2014, TAS-102 was approved in Japan. However, in these pivotal trials, there were few cases in which regorafenib was administered as prior treatments, and also there were few reports on the effectiveness and safety of TAS-102 after administration of regorafenib. Methods: We retrospectively analyzed the clinical data of 126 patients who received TAS-102 after administration of regorafenib in the multi-institutional retrospective study (HGCSG1503). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients characteristics were as follows; male/female 75/51, median age 66.5 (range 38-84), ECOG PS (0/1/2/3) 48/64/12/2, KRAS Exon2 wild/mutant 64/60 (2 patients; KRAS Exon2 was not tested). The initial starting dose was 70 mg/m2 (n = 100, 79.4%) and reduced dose (n = 26, 20.6%). Dose reductions were required in 30 patients (30.9%). The common ≥grade 3 AEs were neutrophil count decreased (45.1%), white blood cell decreased (34.9%), and anemia (28.6%). RR and DCR were 0% and 36.5%, respectively. Median PFS and OS were 2.1 and 5.7 months. In the analysis on the relationship between ECOG PS 0-1 and PS 2-3, median PFS was 2.2 vs. 1.4 months (HR 2.187, p = 0.008), and MST was 6.5 vs. 2.7 months (HR 2.424, p = 0.002). Conclusions: In this analysis, TAS-102 after administration of regorafenib in the real-world clinical practice showed similar efficacy and safety to the pivotal clinical trials, except for patients with PS 2-3. Clinical trial information: 000020551.

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

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