Outcomes in patients (pts) aged ≥65 years in the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1011-1011
Author(s):  
Kevin Kalinsky ◽  
Mafalda Oliveira ◽  
Tiffany A. Traina ◽  
Sara M. Tolaney ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Best Response ◽  
Significant Survival ◽  
Independent Review ◽  
Grade 3 ◽  
The Impact

1011 Background: Approximately 20% of pts diagnosed with TNBC are aged ≥65 y. Often, older pts are less fit for chemotherapy due to a greater rate of comorbidities, increased use of medications, and pre-existing frailty or functional loss. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. The landmark phase 3 ASCENT study (NCT02574455) showed improved outcomes with SG vs single-agent chemotherapy of physician’s choice (TPC) in pts with relapsed/refractory mTNBC (median progression-free survival [PFS], 5.6 vs 1.7 mo; median overall survival [OS], 12.1 vs 6.7 mo). Here we assess the impact of age on the efficacy and safety of SG in ASCENT. Methods: Pts with mTNBC refractory/relapsing after ≥2 prior chemotherapies were randomized 1:1 to receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Safety outcomes were assessed in all treated pts. This prespecified subgroup analysis assessed the impact of age (pts ≥65 y) on PFS, OS, and safety. Results: Of 529 pts enrolled, 468 were BMNeg (median age, 54 y); of these, 44/235 pts (19%) who received SG and 46/233 pts (20%) who received TPC were aged ≥65 y. SG treatment improved median PFS vs TPC in pts ≥65 y (7.1 vs 2.4 mo; HR, 0.22; 95% CI, 0.12-0.40). SG vs TPC treatment also improved median OS in pts ≥65 y (15.3 vs 8.2 mo; HR, 0.37; 95% CI, 0.22-0.64). Treatment with SG vs TPC resulted in higher ORR (50% vs 0%) and clinical benefit rate (CBR, 61% vs 9%) in pts ≥65 y. Of the 7 pts ≥75 y who received SG, 2 had partial response, 4 had stable disease [SD], and 1 had SD > 6 mo as best response. In pts < 65 y, median PFS for SG vs TPC was 4.6 vs 1.7 mo (HR, 0.46; 95% CI, 0.35-0.59), and median OS was 11.2 vs 6.6 mo (HR, 0.50; 95% CI, 0.40-0.64), respectively; the ORR and CBR were 31% vs 6% and 41% vs 9%, respectively. Pts ≥65 y treated with SG vs TPC had similar rates of all grade and grade ≥3 treatment-emergent adverse events (TEAEs). TEAEs leading to dose reduction were similar in pts ≥65 y in the SG vs TPC arms (35% vs 33%) and were lower in pts < 65 y (19% vs 24%). Key treatment-related TEAEs leading to dose reduction in pts ≥65 y in the SG vs TPC arms were neutropenia (including febrile neutropenia; 14% vs 25%), fatigue (10% vs 4%), diarrhea (6% vs 0%), and nausea (4% vs 0%). TEAEs leading to treatment discontinuation with SG vs TPC were low in pts ≥65 y (2% vs 2%) and < 65 y (5% vs 6%). There were no treatment-related AEs leading to death in any SG-treated age group. Conclusions: Irrespective of age, pts who received SG had a significant survival benefit vs TPC, with a tolerable safety profile. Proactive AE monitoring and management will allow optimal therapeutic exposure to SG in older pts. Clinical trial information: NCT02574455 .

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Joyce O'Shaughnessy ◽  
Kevin Punie ◽  
Mafalda Oliveira ◽  
Filipa Lynce ◽  
Sara M. Tolaney ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Chemotherapy Agent ◽  
Recist 1.1 ◽  
Duration Of Response ◽  
Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

2021 ◽  
pp. 107815522110179
Author(s):  
Olivia R Court
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Free Survival ◽  
Length Of Treatment ◽  
Common Grade ◽  
Grade 3 ◽  
The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

Irinotecan plus S-1 (IRIS) versus S-1 alone as first line treatment for advanced gastric cancer: Preliminary results of a randomized phase III study (GC0301/TOP-002)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
K. Chin ◽  
H. Iishi ◽  
H. Imamura ◽  
O. Kobayashi ◽  
H. Imamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Survival ◽  
Single Agent ◽  
Rest Period ◽  
Phase Iii ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
Gastric Cancer Patients

4525 Background: Irinotecan has single agent activity and combination activity with S-1 reportedly in phase I/II studies with advanced gastric cancer patients (pts). S-1, oral fluoropyrimidine, also has activity on gastric cancer. A multicenter, randomized phase III trial comparing IRIS to S-1 alone in advanced gastric cancer was conducted. Methods: Pts with previously untreated gastric cancer were randomized to Arm A (oral S-1 80 mg/m2/day from day 1 to 28 followed by a 14-day rest period), or Arm B (oral S-1 80 mg/m2/day from day 1 to 21 and intravenous irinotecan 80 mg/m2 on days 1 and 15 followed by a 14-day rest). Treatment was continued unless disease progression was observed. Inclusion criteria: PS (ECOG) of 0 to 2; adequate major organ functions. Primary endpoint was overall survival. Results: From June 2004 to November 2005, 326 pts were randomized to arm A (162 pts) and arm B (164 pts). Pts characteristics (arm A vs. arm B) were as follows: median age: 63 vs. 63 years, PS 0–1: 97% vs. 97%, and distribution of subtype of intestinal/diffuse/others: 44%/55%/1% vs. 41%/58%/1%. Among 187 RECIST-evaluable pts (93 vs 94) reviewed by independent review panel, best response rates were 26.9% for arm A and 41.5% for arm B(p=0.035). Among 319 toxicity-evaluable patients (161 vs 158), grade 3 or 4 toxicities for arm A vs arm B (% of pts) were as follows: neutropenia 9.3% vs 26.6%, diarrhea 5.6% vs 15.8%, anorexia 9.9% vs 15.8%, nausea 3.7% vs 7.0%, vomiting 0.6% vs 2.5%. Conclusions: IRIS is effective, and well tolerated in pts with advanced gastric cancer. Survival analysis is underway. No significant financial relationships to disclose.

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]

PALETTE: A randomized, double-blind, phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy—An EORTC STBSG Global Network Study (EORTC 62072).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA10002-LBA10002 ◽  
Author(s):  
W. T. Van Der Graaf ◽  
J. Blay ◽  
S. P. Chawla ◽  
D. Kim ◽  
B. Bui Nguyen ◽  
...  
Keyword(s):  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Global Network ◽  
Phase Iii ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Independent Review ◽  
Grade 3

LBA10002 Background: Pazopanib, a multi targeted angiogenesis inhibitor, has demonstrated single-agent activity in pts with advanced STS. The efficacy and safety of pazopanib versus placebo as second or later line treatment were evaluated in pts with metastatic STS in a multi-center, international, double-blind, placebo-controlled phase III trial. Methods: Pts ≥18 years of age with angiogenesis inhibitor-naïve, histologically proven, metastatic STS, who failed at least one anthracycline containing regimen, could enter the study. They should have ≥1 measurable baseline lesion (per RECIST v1.0), WHO PS 0-1, adequate bone marrow, coagulation, hepatic and renal function, no poorly controlled hypertension, no bleeding diathesis, and no CNS involvement. The study has been conducted by EORTC and GSK in collaboration with 72 sarcoma centers worldwide. Pts were randomized 2:1 to receive either pazopanib 800 mg once daily or placebo until tumor progression, unacceptable toxicity, death, or pt’s request. Results: A total of 369 randomized pts (246 pazopanib, 123 placebo), median age of 56 years, participated in the study (EORTC 45 %, other 55%). Median duration of follow-up at clinical cut-off date is 15 months. The primary endpoint of progression-free survival (PFS) per independent review is significantly prolonged with pazopanib (median: 20 vs 7 weeks; HR=0.31, 95% CI 0.24-0.40 ; P<0.0001). The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo (median: 11.9 vs 10.4 months, HR=0.83, 95% CI 0.62-1.09). Main on-therapy grade 3-4 toxicities in the pazopanib vs placebo arm respectively: fatigue (13%, 6%), hypertension (7%, nil), anorexia (6%, nil), and diarrhea (5%, 1%). Similarly, thromboembolic events (grade 3-5 ) (3%, 2%), LVEF drop of >15% (8%, 3%). Median relative dose intensity of pazopanib was 768 mg daily. Conclusions: Pazopanib is an active drug in anthracycline pretreated metastatic STS pts with an increase in median PFS of 13 weeks.

Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC).

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA8505-LBA8505 ◽  
Author(s):  
Charles M. Rudin ◽  
Maria Catherine Pietanza ◽  
Todd Michael Bauer ◽  
David R. Spigel ◽  
Neal Ready ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Single Agent ◽  
Human Study ◽  
Study Drug ◽  
Antibody Drug Conjugate ◽  
Skin Reactions ◽  
Best Response ◽  
Duration Of Response ◽  
Grade 3 ◽  
Tissue Specimens

LBA8505 Background: SCLC remains among the most deadly of malignancies. Rovalpituzumab tesirine is a first-in-class ADC comprised of a humanized monoclonal antibody against DLL3, a dipeptide linker, and a pyrrolobenzodiazepine (PBD) dimer toxin. DLL3 is highly expressed in neuroendocrine tumors, including approximately 80% of SCLC. The emerging results of the SCLC patients (pts) in a first-in-human study (NCT01901653) are reported here. Methods: Pts with progressive SCLC after at least 1 previous systemic therapy were eligible. Efficacy was assessed by the investigator via RECIST v1.1, and toxicity graded per CTCAE v4.03. When available, archived tumor tissue was assessed retrospectively for DLL3 expression by immunohistochemistry. Results: Seventy-four (74) pts were enrolled at dose levels ranging from 0.05 to 0.8 mg/kg at either q3w or q6w. Among evaluable pts treated at doses of 0.2-0.4 mg/kg, 15/61 (25%; 95% CI 15-37%) achieved a best response of PR or CR, and 44/61 (72%; 95% CI 59-83%) achieved clinical benefit (best response of at least SD). Among pts with available archive tissue specimens and ≥ 50% of cells expressing DLL3 (DLL3hi, an intended companion diagnostic cutoff), 12/22 (55%; 95% CI 32-76%) achieved a best response of PR or CR, and 20/22 (91%; 95% CI 71-99%) achieved clinical benefit, with a median overall survival of 8 (range 1-18+) months. In 3rd line DLL3hi pts (n = 10), where no approved therapy currently exists, the ORR and CBR were 70% and 90%, respectively, with at least 4 evaluable pts achieving OS of > 6 (8, 15, 18 and 18) months. Among responders treated at the phase 2 dose of 0.3 mg/kg, the median duration of response was 6 (range 1-8+) months. Among all SCLC pts, the most common grade 3+ toxicities considered study drug-related have included serosal effusions (14%), thrombocytopenia (12%) and skin reactions (8%). Conclusions: With manageable toxicity, rovalpituzumab tesirine demonstrates encouraging single-agent anti-tumor activity and durability in recurrent or refractory SCLC. A single-arm pivotal study in 3rd line DLL3-expressing SCLC has been initiated. Clinical trial information: NCT01901653.

scholarly journals Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2365
Author(s):  
Charline Lafayolle de la Bruyère ◽  
Pierre-Jean Souquet ◽  
Stéphane Dalle ◽  
Pauline Corbaux ◽  
Amélie Boespflug ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Glucocorticoid Administration ◽  
Grade 3 ◽  
The Impact

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

Inotuzumab Ozogamicin In Combination With Low-Intensity Chemotherapy (Mini-hyper-CVD) As Frontline Therapy For Older Patients (≥60 years) With Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1432-1432 ◽  
Author(s):  
Nitin Jain ◽  
Susan O'Brien ◽  
Deborah A. Thomas ◽  
Elias Jabbour ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Hematological Toxicity ◽  
Intensive Chemotherapy ◽  
Antibody Drug Conjugate ◽  
Inotuzumab Ozogamicin ◽  
Low Intensity ◽  
Grade 3

Abstract Background Older patients (pts) with ALL have a significantly worse outcome. This is primarily due to poor tolerance of intensive chemotherapy. Addition of targeted non-myelosuppressive therapy to effective low-intensity chemotherapy might improve outcome. CD22 expression occurs in >90% of pts with ALL. Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody bound to a toxin, calecheamicin, and has shown single-agent activity in relapsed/refractory ALL (Kantarjian et al. Lancet Oncology 2012). Methods Pts ≥60 years (yrs) with newly-diagnosed B-cell ALL were eligible. The chemotherapy was lower intensity than conventional hyper-CVAD and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses). Rituximab and intrathecal chemotherapy were given for first 4 courses. IO was given on day 3 of each of the first 4 courses. The first 6 pts received 1.3 mg/m2 for cycle 1 followed by 0.8 mg/m2 for subsequent cycles; pts 7 onwards received 1.8 mg/m2 for cycle 1 followed by 1.3 mg/m2 for subsequent cycles. Results Fifteen pts (10 men, 5 women) have been treated so far. Median age is 69 yrs (range 60-79). Median follow-up is 10.8 months (mos). Grade 3-4 non-hematological toxicity included 2 pts with grade 3 LFT elevation. Eleven pts had one or more infections. Six patients were switched early to maintenance therapy due to thrombocytopenia. No dose-limiting toxicity was observed. Of the 14 patients evaluable for response (one patient started with CR that she had achieved with single-agent prednisone), 13 patients (93%) achieved CR/CRp (12 CR, 1 CRp). All pts achieving CR have also achieved flow-cytometric MRD negative status and all except one continue to be on study in CR anywhere from 0.1 to 19.2 mos. There has been one relapse in a patient who received only 3 intensive chemotherapy cycles due to prolonged thrombocytopenia. She relapsed at the 1-year mark and is currently receiving salvage chemotherapy. One patient did not achieve CR and died 2 mos later after receiving a salvage regimen. This is the only death on the study. One-year disease-free and overall survival are 83% and 93%, respectively. Conclusions The combination of IO with low-intensity mini-hyper-CVD chemotherapy is safe and shows very encouraging results (93% CR/CRp) in the frontline setting in older pts with ALL. These results appear to be better than those achieved with a chemotherapy only approach and may become the new standard of care for frontline treatment of older pts with ALL. Disclosures: Off Label Use: Inotuzumab is a antibody drug conjugate targeting CD22 on ALL cells. Ravandi:Pfizer: Honoraria. Kantarjian:Bristol-Myers Squibb, Novartis, Pfizer: Research Funding.

Phase II Trial of Perifosine (KRX-0401) in Relapsed and/or Refractory Waldenström Macroglobulinemia: Preliminary Results.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4493-4493 ◽  
Author(s):  
Irene M. Ghobrial ◽  
Xavier Leleu ◽  
Nancy Rubin ◽  
Marybeth Nelson ◽  
Renee Leduc ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Hemolytic Anemia ◽  
Phase Ii ◽  
Single Agent ◽  
Akt Inhibitor ◽  
Best Response ◽  
M Spike ◽  
Grade 3

Abstract INTRODUCTION: Perifosine is an oral, novel synthetic alkylphospholipid, with multiple effects on signal transduction pathways, including inhibition of Akt. We previously demonstrated that AKT is upregulated in samples of patients with WM and that the AKT inhibitor perifosine induces significant growth inhibition in vitro and in vivo in xenograft models in WM. Phase I trials with perifosine have demonstrated a favorable side effect profile. This phase II study aimed to determine safety and activity of the oral AKT inhibitor perifosine in patients with relapsed/refractory WM. METHODS: Patients who had at least one previous therapy for WM and who had relapsed or refractory disease were eligible. NCI CTCAE v3.0 was used for toxicity assessment. Response was assessed by criteria established at the second consensus panel for WM. All patients received 150 mg perifosine daily for 28 days per cycle for 6 cycles; response was assessed after 2 cycles. RESULTS: 28 pts (20 men and 8 women, median age 64.8 years, range 51 – 80) have been treated to date. The median number of lines of prior treatment was 2 (range 1 – 5). The median IgM at baseline was 3245 mg/dL (range 972– 8480); median M-spike at baseline was 1.9 g/dL (range 0.5 – 4.85); and median hemoglobin was 11.3 g.dL (7.0–14.0). The median follow up was 5 months (range 1 – 8 months). Prior therapy included rituximab, nucleoside analogues (fludarabine and 2-CDA), combination chemotherapy (e.g CHOP, CVP), chlorambucil. and bortezomib. 21 pts are currently evaluable for response, best response to single agent perifosine after 2 cycles are presented in Table 1. Median duration of response has not been reached. None of the patients progressed while on therapy with perifosine. The median M spike reduction was 20% (0 – 76). Patients tolerated perifosine well without significant toxicities: grade 3 nausea/vomiting in 1 patient resolved with dose reduction to 100 mg; grade 3 anemia in one patient was related to cold-agglutinin hemolytic anemia; and 2 patients had GI bleeding unrelated to therapy. Dose reduction (to 100 mg/d) was required in 4 patients; 2 for nausea and loss of weight, 1 for non-specific bone pain and 1 for an episode of fever and fatigue. Four patients discontinued therapy, one for cold-aggutinin related hemolytic anemia related to WM, one due to corneal ulceration that was possibly related to perifosine and corneal infection, and 2 for patient decision. Attributable toxicities otherwise proved manageable with appropriate supportive care and perifosine was generally well tolerated, with no peripheral neuropathy. CONCLUSIONS: Oral perifosine as monotherapy has been well tolerated and demonstrates encouraging activity achieving PR + MR in 34%, and/or stabilization of disease in 66% of evaluable patients with relapsed WM. Updated data will be presented at the meeting. Table 1 Response N=21; ORR (CR+PR+MR)=34% Median time to best response (months) Partial response 2(10%) 5 Minimal response 5 (24%) 4 (3–6) Stable Disease (SD) 14 (66%) NA Progressive Disease 0

Results of GROC-rev salvage regimen: Gemcitabine, rituximab, and oxaliplatin chemotherapy with revlimid for relapsed/refractory aggressive non-Hodgkin lymphoma (NHL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7556-7556 ◽  
Author(s):  
Fernando Cabanillas ◽  
Idalia Liboy ◽  
Alexis Cruz ◽  
Pedro Gil Solivan ◽  
Noridza Rivera ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Regimen ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Best Response ◽  
Grade 3 ◽  
Clinical Trial Information

7556 Background: Currently there is no optimal salvage regimen for relapsed/refractory NHL (R/R NHL). Prognosis of pts who fail to achieve CR to salvage therapy is dismal. We sought to improve the CR rate by adding Lenalidomide (L) to GROC (ASCO #8530, 2008). Methods: Primary endpoint was rate of conversion to CR after switch to L for pts whose best response to GROC was <CR. Secondary endpoint was progression free survival (PFS) of all pts as well as those who achieve <CR on chemotherapy and were crossed over to L.Pts who failed to achieve at least PR after GROC x2 and those who didn’t achieve CR after GROC x6, were crossed over to L 25 mg x 3 weeks q 28 days. CRs were maintained on L x 2 yrs. Results: 34 pts were enrolled of which 32 are evaluable. Median age: 61 and 56% males. Histologies included DLBCL (81%), PTCL (9%), follicular grade 3-B (9%). Stage was III-IV in 75% and median IPI=2. Best overall response rate (ORR) at any point during treatment= 19/32 (59%) and CR 13/32 (41%). ORR before crossover to L=13/32 (41%) and CR= 8/32 (25%). There were 24 who failed to achieve CR on GROC (19 who didn’t respond at all and 5 whose maximum response was PR). Of these, 21 crossed over to L and 7 (33%) responded (CR in 5, PR in 2). The fact that 5 pts attained a CR to L thus improving the CR rate from 25% to 41% after exhibiting refractoriness to GROC is noteworthy. Of the 7 responders to L, all are alive and only 1 relapsed. At 2 yrs., overall survival (OS) was 48% and PFS 35%. This compares favorably with our previous GROC study without L in which 2 yr. OS= 33% and PFS 29%. In total, 11 pts were eligible for ASCT after chemo plus L and 8 were transplanted (3 refused). Of these eight, 6 remain in CR at 11, 18, 21, 22, 52, 74 mos. At 2 yrs, PFS for transplanted pts is 73% and for those whose response to GROC before crossover to L was <CR, it is 27 mos. Toxic events included 2 neutropenic fevers, 1 MDS (34 mos. after ASCT) and 1 AML (11 mos. after ASCT). Both of these remain continuously in CR after allo SCT. Conclusions: 2 yrOS=48% and PFS=35% with GROC-Rev are the best observed with any salvage regimen we have tested. L is active as a single agent in 29% of cases whose best response to GROC was <CR. A larger study is desirable to confirm these data. Clinical trial information: NCT01307592.

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