Adverse events (AEs) with maintenance olaparib tablets in patients (pts) with BRCA-mutated (BRCAm) platinum-sensitive relapsed serous ovarian cancer (PSR SOC): Phase III SOLO2 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5518-5518 ◽  
Author(s):  
Jonathan A. Ledermann ◽  
Alain Lortholary ◽  
Richard T. Penson ◽  
Emma Gibbs ◽  
Diane M. Provencher ◽  
...  
Keyword(s):  
Parp Inhibitor ◽  
Phase Iii ◽  
Low Grade ◽  
Platinum Sensitive ◽  
Treatment Dose ◽  
Common Grade ◽  
Grade 3 ◽  
Platinum Chemotherapy ◽  
Dose Reductions ◽  
Clinical Trial Information

5518 Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance therapy with the PARP inhibitor olaparib significantly improved PFS vs placebo (PBO) in BRCAm PSR SOC pts (HR 0.30, 95% CI 0.22–0.41, P<0.0001; median 19.1 vs 5.5 months) and was well tolerated (Pujade-Lauraine et al, SGO 2017). We analyzed AEs in SOLO2, the first study in PSR SOC to use the olaparib tablet formulation. Methods: Pts with BRCAm PSR SOC, who were in response to platinum chemotherapy, were treated with olaparib (300 mg bid; tablets; n=195) or PBO (n=99) until progression. AEs were graded by CTCAE v4.0. Results: The most common AEs with olaparib – nausea, fatigue/asthenia, anemia, and vomiting – were largely grade 1–2, though anemia was the most common grade ≥3 AE. AEs of fatigue/asthenia, vomiting and nausea generally improved as treatment continued, though fatigue/asthenia and anemia could last for several months (table). Most AEs were manageable by supportive treatment, dose interruptions (olaparib, 45%; PBO, 18%) and dose reductions (olaparib, 25%; PBO, 3%). Discontinuation of olaparib due to AEs was minimal (11%); anemia and neutropenia were the only AEs leading to discontinuation of olaparib in >one pt. Conclusions: Most AEs experienced by pts receiving olaparib tablets in SOLO2 were low grade and manageable. Initial nausea, vomiting and fatigue generally improved with ongoing treatment. The majority of AEs first occurred within the first three months of treatment. AEs causing treatment discontinuation were rare and mainly hematological. Clinical trial information: NCT01874353. [Table: see text]

Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5506-5506 ◽  
Author(s):  
Richard T. Penson ◽  
Ricardo Villalobos Valencia ◽  
David Cibula ◽  
Nicoletta Colombo ◽  
Charles A. Leath ◽  
...  
Keyword(s):  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Platinum Sensitive ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Platinum Chemotherapy

5506 Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m2 D1, D8, D15 q4w] or PLD [50 mg/m2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs >12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [ PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P=0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P=0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P<0.001; median 13.2 vs 8.5 months, respectively). Most common adverse events (AEs) with olaparib were nausea (65% vs 34% [TPC]) and anemia (50% vs 25%) and with TPC were palmar-plantar erythrodysesthesia (PPE; 36% vs 1% [olaparib]) and nausea. Most common grade ≥3 AEs in either arm were anemia (21% [olaparib] vs 0 [TPC]), PPE (0 vs 12%) and neutropenia (6% vs 11%). For olaparib vs TPC, serious AEs were reported by 24% vs 18% and AEs led to treatment discontinuation in 7% vs 20%. Conclusions: Pts with gBRCAm PSR OC receiving olaparib monotherapy had a significant, clinically relevant improvement in ORR and PFS vs TPC, with no new safety signals. Clinical trial information: NCT02282020.

Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (SOC) and a BRCA mutation (BRCAm).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5505-5505 ◽  
Author(s):  
Jonathan A. Ledermann ◽  
Philipp Harter ◽  
Charlie Gourley ◽  
Michael Friedlander ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Phase Iii ◽  
Double Blind ◽  
Platinum Sensitive ◽  
Trial Outcome Index ◽  
Phase Iii Trials ◽  
Outcome Index ◽  
Clinical Trial Information

5505 Background: Previously, we reported that maintenance treatment with the oral PARP inhibitor olaparib (400 mg bid) led to a significant PFS improvement vs placebo in patients (pts) with platinum-sensitive relapsed SOC (Ledermann et al NEJM2012). A preplanned subgroup analysis from this randomized, double-blind Phase II trial (NCT00753545) suggested that olaparib may lead to a greater PFS, and an OS, benefit in pts with a known germline BRCAm (gBRCAm). Since gBRCA wild-type (gBRCAwt) pts may develop somatic tumor (t)BRCAm, efficacy analyses were performed for all pts with BRCAm. Methods: gBRCAm status was determined retrospectively for all consenting pts (n = 166) using blood samples taken before randomization. tBRCAm status was determined from archival tumor samples of 196 pts. We analyzed PFS/OS by gBRCAm and total BRCAm status. Preliminary data are reported. Results: gBRCA status was known for 218/265 pts (gBRCAm, 96; gBRCAwt, 122). Including tBRCAm, 136 pts had a BRCAm (BRCAwt, 116). gBRCAm pts had the greatest PFS benefit with olaparib maintenance vs placebo (median: 11.2 vs 4.1 months [m]; HR, 0.17; 95% CI 0.09-0.32; P<0.001) and a significant QoL improvement, as measured with Trial Outcome Index (OR, 4.08; 95% CI 1.11-19.85; p = 0.03). The PFS benefit was consistent when tBRCAm pts were included (median: 11.2 vs 4.3 m; HR, 0.19; 95% CI 0.11-0.32; p <0.0001). In an interim analysis of OS (58% maturity), a comparison of olaparib vs placebo in the overall population led to a HR of 0.88 (95% CI 0.64-1.21) with medians of 29.8 vs 27.8 m, respectively. Although HRs from the gBRCAm and gBRCAwt subgroups were similar (0.85 and 0.84, respectively), 13/37 gBRCAm placebo pts received a subsequent PARP inhibitor, confounding the OS data in this subgroup. The analysis of all BRCAm pts was less confounded and resulted in an OS HR of 0.74 (95% CI 0.46-1.19; median: 34.9 vs 31.9 m). 19 pts have received olaparib for >3 years. Olaparib tolerability was similar in BRCAm pts and the overall population. Conclusions: Olaparib maintenance treatment led to the greatest clinical benefit in pts with a BRCAm. These compelling data warrant confirmation in phase III trials. Clinical trial information: NCT00753545.

NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14640-e14640
Author(s):  
Anita Ahmed Turk ◽  
Ticiana Leal ◽  
Nancy Chan ◽  
Robert Wesolowski ◽  
Kristen Renee Spencer ◽  
...  
Keyword(s):  
Phase 1 ◽  
Parp Inhibitor ◽  
Parp Inhibition ◽  
Tumor Type ◽  
Strand Breaks ◽  
Grade 5 ◽  
Common Grade ◽  
Grade 3 ◽  
Dna Strand ◽  
Platinum Chemotherapy

e14640 Background: Poly(ADP-ribose) polymerase (PARP) enzymes are involved in DNA repair and activated by DNA strand breaks. DNA damage from carboplatin is associated with activation of PARP. Preclinical data indicate that PARP inhibition and trapping potentiates the anti-tumor effect of platinum chemotherapy. Talazoparib (T) is an oral, selective PARP inhibitor. This phase I study combines T with carboplatin (C) and paclitaxel (P). Methods: Two dosing schedules are being investigated. C is administered on day 1 and P on days 1, 8, and 15 of a 21-day cycle. T (100-1000mcg) is dosed once daily for days 1-7 (schedule A) or days 1-3 (schedule B). Dose escalation is by 3+3 design. Patients (pts) must have tumor type that is expected to respond to C + P or have BRCA germline or somatic mutation and adequate organ function. After 4-6 cycles of combination therapy, pts may continue the combination, change to C and intermittent T without P or change to T alone. Each schedule will have a 6 pt dose expansion at the MTD. The dose level (DL) 1 for schedule B is the previously reported MTD from schedule A (T 250mcg with C AUC 6 + P 80mg/m2). Results: Schedule B results are reported: 15 pts (median age 56 yrs [range 43-76]) have been enrolled. Primary malignancies include colorectal (4), pancreas (4), prostate (2), urothelial (2), and other (3). Dose was initiated at Schedule A MTD. DL2 (T 350mcg with C AUC 6 + P 80mg/m2) exceeded the MTD with 2 of 6 pts experiencing hematologic dose limiting toxicities (DLTs). DL1 is the confirmed schedule B MTD. Dose expansion to 6 pts is ongoing. Of the 11 pts with measurable disease, 3 (27%) had PR and 5 (45%) had SD. Pts were on study a median of 10 weeks (range 5-36+). Most common grade 3/4 AEs include leukopenia (53%), neutropenia (47%), and anemia (47%). One grade 5 AE of intracranial hemorrhage occurred, possibly related to therapy in the setting of grade 3 thrombocytopenia and concern for CNS disease. Conclusions: The schedule B MTD and RP2D is T 250 mcg with C AUC 6 and P 80mg/m2. Data from the full dose expansion will be presented. This combination was tolerated with prolonged responses seen at lower dose T in combination with C+P. Clinical trial information: NCT02317874.

Final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy (chemo) with or without pembrolizumab (pembro) in patients (pts) with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9582-9582
Author(s):  
Delvys Rodriguez-Abreu ◽  
Steven Francis Powell ◽  
Maximilian Hochmair ◽  
Shirish M. Gadgeel ◽  
Emilio Esteban ◽  
...  
Keyword(s):  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Primary Endpoints ◽  
Improved Outcomes ◽  
Grade 3 ◽  
Platinum Chemotherapy ◽  
To Receive ◽  
Clinical Trial Information ◽  
Nonsquamous Nsclc

9582 Background: The phase III KEYNOTE-189 study (NCT02578680), showed significant improvements in OS and PFS with pembro + chemo vs placebo + chemo in pts with previously untreated metastatic nonsquamous NSCLC without sensitizing EGFR/ALK mutations. We report the protocol-specified final analysis of KEYNOTE-189. Methods: Pts were randomized 2:1 to receive 35 cycles of pembro 200 mg Q3W (n = 410) or placebo Q3W (n = 206) plus 4 cycles of pemetrexed (pem) and carboplatin/cisplatin followed by maintenance pem. Pts in the placebo + chemo arm could crossover to pembro upon PD. PFS and OS were primary endpoints; ORR was a secondary endpoint. PFS2 (time from randomization to objective tumor progression on next-line treatment/death), was an exploratory endpoint. Results: At data cutoff (May 20, 2019), median (range) time from randomization to data cutoff was 31.0 (26.5–38.8) mo. 17 pts in the pembro + chemo arm and 1 pt in the placebo + chemo arm were receiving initially assigned treatment; 84 pts crossed over to pembro. Median (95% CI) OS (22.0 [19.5–24.5] vs 10.6 [8.7–13.6] mo; HR 0.56 [95% CI, 0.46–0.69]) and PFS (9.0 [8.1–10.4] vs 4.9 [4.7–5.5] mo; HR 0.49 [95% CI, 0.41–0.59]) were longer with pembro + chemo vs placebo + chemo (Table). The 2-y OS rate was 45.7% vs 27.3% and the 2-y PFS rate was 22.0% vs 3.4%. ORR was 48.3% with pembro + chemo vs 19.9% with placebo + chemo. 56 pts in the pembro + chemo arm completed 35 cycles of pembro among whom ORR was 85.7% (4 CR, 44 PR, 8 SD) and median OS was not reached. 292 (72.1%) pts in the pembro + chemo arm and 135 (66.8%) pts in the placebo + chemo arm had grade 3–5 AEs. Conclusions: Pembro + chemo continued to show improved outcomes in OS, PFS, ORR and PFS2 compared with placebo + chemo, with manageable toxicity. These findings support first-line pembro + chemo in pts with previously untreated metastatic nonsquamous NSCLC. Clinical trial information: NCT02578680 . [Table: see text]

scholarly journals COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3573
Author(s):  
Alfred Chung Pui So ◽  
Harriet McGrath ◽  
Jonathan Ting ◽  
Krishnie Srikandarajah ◽  
Styliani Germanou ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Safety Data ◽  
Vaccine Safety ◽  
Phase Iii ◽  
Solid Malignancy ◽  
Common Grade ◽  
Phase Iii Trials ◽  
Oncology Care ◽  
Grade 3 ◽  
Oncology Centre

Emergency approval of vaccines against COVID-19 provides an opportunity for us to return to pre-pandemic oncology care. However, safety data in cancer patients is lacking due to their exclusion from most phase III trials. We included all patients aged less than 65 years who received a COVID-19 vaccine from 8 December 2020 to 28 February 2021 at our London tertiary oncology centre. Solicited and unsolicited vaccine-related adverse events (VRAEs) were collected using telephone or face-to-face consultation. Within the study period, 373 patients received their first dose of vaccine: Pfizer/BioNTech (75.1%), Oxford/AstraZeneca (23.6%), Moderna (0.3%), and unknown (1.1%). Median follow-up was 25 days (5–85). Median age was 56 years (19–65). Of the patients, 94.9% had a solid malignancy and 76.7% were stage 3–4. The most common cancers were breast (34.0%), lung (13.4%), colorectal (10.2%), and gynaecological (10.2%). Of the patients, 88.5% were receiving anti-cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed any grade VRAE of which 2.1% were grade 3. No grade 4/5 or anaphylaxis were observed. The most common VRAEs within 7 days post-vaccination were sore arm (61.7%), fatigue (18.2%), and headaches (12.1%). Most common grade 3 VRAE was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in oncology patients have mild reactogenicity.

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Andres Poveda ◽  
Stephanie Lheureux ◽  
Nicoletta Colombo ◽  
David Cibula ◽  
Kristina Lindemann ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib ◽  
Grade 3

5545 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]

scholarly journals Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

2014 ◽  
Vol 32 (25) ◽  
pp. 2735-2743 ◽  
Author(s):  
Ezra E.W. Cohen ◽  
Theodore G. Karrison ◽  
Masha Kocherginsky ◽  
Jeffrey Mueller ◽  
Robyn Egan ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Distant Failure ◽  
Common Grade ◽  
Treatment Naïve ◽  
Grade 3

Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.

Bortezomib Added to CVP-R Is Safe and Effective for Previously Untreated Advanced Stage Follicular Lymphoma: A Phase II Study by the NCIC Clinical Trials Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 407-407
Author(s):  
Laurie H. Sehn ◽  
David A Macdonald ◽  
Sheldon H. Rubin ◽  
Guy Cantin ◽  
Morel Rubinger ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Research Funding ◽  
Standard Dose ◽  
Phase Iii ◽  
High Risk Population ◽  
Low Grade ◽  
Grade 3 ◽  
To Receive ◽  
Experienced Grade

Abstract Abstract 407 Background: Bortezomib, the first-in-class proteasome inhibitor has demonstrated promising efficacy as a single agent in heavily pretreated patients (pts) with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of the addition of bortezomib to cyclophosphamide, vincristine, prednisone and rituximab (CVP-R), one of the most commonly used regimens in untreated patients. Methods: This is a phase II multi-centre open-label trial adding bortezomib (1.3 mg/m2 day 1&8) to standard dose cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2, capped at 2 mg), prednisone (40 mg/m2 × 5) and rituximab (375 mg/m2) for up to 8 cycles in pts with newly diagnosed stage III/IV FL requiring therapy. Response was assessed following 4 and 8 cycles. The two co-primary endpoints were complete response rate (CR/CRu) and incidence of grade 3/4 neurotoxicity. Following the final response assessment, patients were permitted to receive maintenance rituximab at the discretion of the treating physician according to local practice. Results: Between March 2007 and February 2009, 95 patients were enrolled. Median age was 56.6 years (range 29.5 – 83.6 years). 48% percent were male and 63% had stage IV disease. FLIPI score at study entry: low 11%, intermediate 43%, high 46%. Safety data was availabel on all patients. Overall, the combination of bortezomib and CVP-R was extremely well tolerated. No pts have developed grade 4 neurotoxicity and only 6/95 (6.3%) have developed grade 3 neurotoxicity (five sensory neuropathy and one neuropathic pain). The incidence of grade I and II neuropathy was 65.3% and 36.8% respectively. Neurotoxicity was largely reversible. Five pts discontinued therapy prematurely (three refused further treatment, one pt was found to have Hodgkin lymphoma as well as FL and one pt was removed from study for non-compliance). 84% of planned bortezomib treatments and 85% of vincristine treatments were administered without dose reduction. Five pts experienced grade 3/4 anemia and 3 pts experienced grade 3/4 thrombocytopenia. Only 4 episodes of febrile neutropenia occurred and 2 grade 3 infections were noted. No grade 4 infections were reported. No serious adverse events were reported. One patient died due to progressive disease. At present, 78/95 patients are evaluable for response. 37/78 (47%) achieved a CR/CRu (95% CI 36.4, 58.5), and 29/78 (37%) achieved a PR with an ORR of 84.6% (95% CI 76.6, 96.6). An additional 5/78 pts had stable disease, while 7/78 progressed on therapy. Complete efficacy data as well as information on quality of life will be availabel within the next few months. Forty-one of 70 pts (58.6%) with availabel follow-up information went on to receive maintenance rituximab. Conclusions: The addition of bortezomib to standard dose CVP-R is feasible and well tolerated with minimal associated toxicity. Neurotoxicity is primarily low grade and reversible and does not limit delivery of either bortezomib or vincristine. The complete remission rate in this high risk population compares favorably to historical results of patients receiving CVP-R. Based on these encouraging results, a phase III trial of CVP-R with or without bortezomib is currently being planned. Disclosures: Sehn: Johnson and Johnson Ortho Biotec: Honoraria. Off Label Use: Velcade for is not yet approved for follicular lymphoma. Chen:Johnson and Johnson Ortho Biotec: Research Funding. Djurfeldt:Johnson and Johnson Ortho Biotec: Research Funding. Shepherd:Johnson and Johnson Ortho Biotec: Research Funding. Crump:Johnson and Johnson Ortho Biotec: Honoraria.

International randomized phase III study of capecitabine (Cap), bevacizumab (Bev), and mitomycin C (MMC) in first-line metastatic colorectal cancer (mCRC): Final results of the AGITG MAX trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4023-4023
Author(s):  
N. C. Tebbutt ◽  
V. Gebski ◽  
K. Wilson ◽  
M. Cummins ◽  
Y. Chua ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Phase Iii ◽  
First Line ◽  
Treatment Regimens ◽  
Intention To Treat ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Low Toxicity ◽  
Grade 3

4023 Background: The addition of Bev to oxaliplatin or irinotecan based doublet chemotherapy has shown benefit in mCRC. Cap± MMC are alternate chemotherapy regimens suitable for patients (pts) who are either unfit for or who do not require initial oxaliplatin/irinotecan. This phase III study compared Cap with Cap Bev and Cap Bev MMC. The aim was to develop a low toxicity regimen suitable for a broad population of pts with mCRC. Methods: Previously untreated pts with unresectable mCRC considered suitable for Cap monotherapy were randomised to arm A Cap (Cap 2000mg/m2/d or 2500mg/m2 d1–14 q21d), arm B Cap Bev (Bev 7.5mg/kg q3w) or arm C Cap Bev MMC (MMC 7mg/m2 q6w). Primary endpoint: PFS, secondary endpoints: RR, toxicity, OS, QoL . Randomisation was stratified by age, PS, centre and Cap dose. Response was assessed every 6w. The study was designed to detect an increase in the median PFS from 5.5m (arm A) to 8m (arm B or C) at p<0.025 with 80% power. Results: A total of 471 pts were randomised from July 2005-June 2007. Outcomes were evaluated on an intention to treat basis and included 15 ineligible pts. Baseline demographics were well balanced between arms with median age 67y (range 31–86y). Toxicity was reported: ASCO 2008 abstr 4029. The most common grade 3/4 toxicities were PPE (16%, 26%, 28%) and diarrhoea (11%, 17%, 16%) for arms (A,B,C). However, adjusted rates per cycle were similar as arms B & C received more cycles of Cap (A8.3, B10.8, C10.5). Other toxicity rates were generally <10%. The study achieved its primary endpoint with a highly significant improvement in PFS for arms B & C. RR and OS are summarized ( Table ). Conclusions: All treatment regimens were well tolerated in a relatively elderly patient cohort. The addition of Bev±MMC to Cap significantly improved PFS without significant additional toxicity. OS was similar for all arms. Cap Bev±MMC is an active, low toxicity regimen that may be considered as a treatment option for pts with mCRC. [Table: see text] [Table: see text]

Safety of ipilimumab in patients (pts) with untreated, advanced melanoma alive beyond 2 years: Results from a phase III study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8512-8512 ◽  
Author(s):  
Luc Thomas ◽  
Jedd D. Wolchok ◽  
Claus Garbe ◽  
Celeste Lebbe ◽  
Igor Bondarenko ◽  
...  
Keyword(s):  
Safety Profile ◽  
Human Monoclonal Antibody ◽  
Survival Rates ◽  
Safety Data ◽  
Advanced Melanoma ◽  
T Cell Response ◽  
Phase Iii ◽  
Low Grade ◽  
Grade 3 ◽  
The Impact

8512 Background: Ipilimumab (IPI), a fully human monoclonal antibody, blocks cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor T-cell response. In a phase 3 study (CA184-024) of previously untreated pts with stage III or IV melanoma, IPI + dacarbazine (DTIC) significantly improved overall survival (OS) vs. DTIC alone (Robert et al. NEJM 2011). We now report safety data of IPI in pts from this study alive > 2 yrs from study initiation. Methods: Pts with untreated advanced melanoma, were randomized to IPI (10 mg/kg) + DTIC (850 mg/m2) or placebo + DTIC (850 mg/m2) given at Wks 1, 4, 7, 10 followed by DTIC q 3 wks through Wk 22. Eligible pts (stable disease or better) received IPI or placebo q 12 wks as maintenance. In the population of subjects alive >2 yrs, the appearance of immune-related adverse events (irAEs) occurring after 2 yrs was evaluated. Within this group was a subset of subjects still receiving IPI dosing after 2 yrs; safety for these pts was evaluated to assess the impact of prolonged IPI exposure. Results: In the IPI + DTIC group 68 (28%) pts survived > 2 yrs compared to 44 (18%) in the DTIC alone group; 11 of the 68 continued IPI dosing for ≥ 2 yrs. Safety assessment beyond 2 yrs showed 3 of the 11 pts had any grade irAEs; 1 pt had grade 3/4 rash, pruritus while low grade events included rash, pruritus (n=2) and elevated ALT / AST (n=1). Overall among all 68 pts in the Ipi + DTIC group, there were 5 pts (7.4%) with any grade irAEs including grade 3/4 rash, pruritus (n=1) and low grade rash (n=3), pruritus (n=2), skin hypopigmentation, and elevated ALT / AST (n=1). No gastrointestinal or endocrine events (any grade) were observed. Conclusions: In Study 024, IPI + DTIC treatment improved OS pts with untreated, advanced melanoma with higher survival rates in the IPI + DTIC group at 1 yr (47.3% vs. 36.3%), 2 yrs (28.5% vs. 17.9%), and 3 yrs (20.8% vs. 12.2%) (HR 0.72, p<0.001). The safety profile of pts alive after 2 yrs suggests that treatment with IPI + DTIC is associated with low rates of irAEs in these pts. Furthermore, in pts still receiving active IPI treatment beyond ≥ 2 yrs, the safety profile appears to be consistent and medically manageable using established safety guidelines (Weber, Oncologist 2007).

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