Long-Term Efficacy and Safety of Ibrutinib in the Treatment of CLL Patients: A Real Life Experience

Ibrutinib has demonstrated a significant clinical impact in patients with de novo and relapsed/refractory chronic lymphocytic leukemia (CLL), even in cases with unfavorable cytogenetics and molecular markers. All CLL patients’ data treated at our Institute with ibrutinib have been retrospectively reviewed. Forty-six patients received ibrutinib either as frontline (10) or second or more advanced treatment (36). Five patients presented with TP53 mutations; 11 had the deletion of chromosome 17p; 17 displayed an unmutated immunoglobulin variable heavy chain status. The median number of cycles administered was 26. Among patients treated frontline, the best overall response rate (ORR) was 90.0%. In patients receiving ibrutinib as a second or later line ORR was 97.2%. Median progression-free survival was 28.8 and 21.1 months for patients treated frontline and as second/later line, respectively. Median overall survival was not reached for those treated frontline and resulted in 4.9 years for patients treated as second/later line. Grade 3–4 hematological toxicities were neutropenia, thrombocytopenia, and anemia. Grade 3–4 extrahematological toxicities included diarrhea, cutaneous rash, utero-vesical prolapse, vasculitis, and sepsis. Ibrutinib is effective and well tolerated in CLL. Responses obtained in a real-life setting are durable and the safety profile of the drug is favorable.

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Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle invasive urothelial bladder cancer (MIUBC): Preliminary results of the GETUG/AFU V05 VESPER trial on toxicity and pathological responses.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.437 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 437-437 ◽

Cited By ~ 4

Author(s):

Stephane Culine ◽

Gwenaelle Gravis ◽

Aude Flechon ◽

Michel Soulie ◽

Laurent Guy ◽

...

Keyword(s):

Progression Free Survival ◽

Median Number ◽

Phase Iii ◽

Perioperative Chemotherapy ◽

Urothelial Bladder ◽

Secondary Endpoints ◽

Grade 3 ◽

Muscle Invasive ◽

Dose Dense ◽

Number Of Cycles

437 Background: The optimal perioperative chemotherapy regimen for patients (pts) with MIUBC is not defined. Methods: Between February 2013 and February 2018, 494 pts were randomized in 28 French centres and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). The primary endpoint was the progression-free survival at 3 years. Secondary endpoints included toxicity, pathological responses and overall survival. Results: In the neoadjuvant group, 218 pts received dd-MVAC and 219 pts GC. The median number of cycles was 6 (0-6) and 4 (1-4), respectively. 60% of pts received 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm. 199 pts (91%) and 198 (90%) pts underwent surgery, respectively. Complete pathologic responses (ypT0pN0) were observed in 84 (42%) and 71 (36%) pts, respectively (p=0.02). An organ-confined status (<ypT3pN0) was obtained in 154 (77%) and 124 (63%) pts, respectively (p=0.002). In the adjuvant group (57 pts), the median number of cycles was 5 (1-6) and 4 (1-4), respectively. 40% of pts received 6 cycles in the dd-MVAC arm, 60% received 4 cycles in the GC arm. Most of CTCAE grade ≥ 3 toxicities concerned hematological toxicities. At least one of these where reported for 125 (50%) pts in the dd-MVAC group and 134 (54%) pts in the GC group (p=NS). Gastrointestinal (GI) grade ≥ 3 disorders were more frequently observed in the dd-MVAC arm (p<0.0001) as well as grade ≥ 3 asthenia (p<0.00001). Four deaths (3 in the dd-MVAC) occurred during chemotherapy. Conclusions: Complete pathological responses and organ-confined status were more frequently observed in the dd-MVAC arm. Toxicity was manageable with more severe asthenia and GI side effects in the dd-MVAC arm. Clinical trial information: 2012-000563-25.

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MEDI3726, a prostate-specific membrane antigen (PSMA)-targeted antibody-drug conjugate (ADC) in mCRPC after failure of abiraterone or enzalutamide.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.99 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 99-99 ◽

Cited By ~ 2

Author(s):

Johann S. De Bono ◽

Mark T. Fleming ◽

Judy Sing-Zan Wang ◽

Richard Cathomas ◽

Marna Williams ◽

...

Keyword(s):

Phase 1 ◽

Progression Free Survival ◽

Circulating Tumor Cell ◽

Median Number ◽

Antibody Drug Conjugate ◽

Starting Dose ◽

Duration Of Response ◽

Grade 3 ◽

Number Of Cycles ◽

Composite Response

99 Background: MEDI3726 is an ADC targeting PSMA. Once bound to PSMA and internalized, the released pyrrolobenzodiazepine dimer toxin crosslinks DNA and triggers cell death. This phase 1 study evaluated the safety and efficacy of MEDI3726 in mCRPC after failure of abiraterone and/or enzalutamide and a taxane-based therapy. Methods: The starting dose was 0.015 mg/kg MEDI3726 IV Q3W until disease progression or unacceptable toxicity. Dose escalation used a modified toxicity probability interval algorithm (mTPI). The primary objectives were safety, adverse events (AEs) and dose-limiting toxicities (DLTs) and to determine the maximum tolerated (MTD) or administered (MAD) dose. Secondary objectives included antitumor activity, pharmacokinetics and immunogenicity. The endpoint for activity was composite response: confirmed response by RECIST v1.1, and/or PSA decrease of ≥ 50% after ≥ 12 wks, and/or confirmed conversion in circulating tumor cell count, defined as a decrease from ≥ 5 to < 5 cells/7.5 mL. Efficacy analyses were based on Prostate Working Group Criteria. Mutational profiles were evaluated in ctDNA. Results: As of Sept 27 2019, 33 pts received MEDI3726. Median age was 71.0 yr. Median number of prior regimens was 4. Median follow-up was 5.4 mo. Drug-related AEs occurred in 30 (90.9%), being grade 3/4 in 15 (45.5%), serious in 11 (33.3%) and causing discontinuation in 13 (39.4%). There were no drug-related deaths. One pt at 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. No MTD was identified per mTPI; the MAD was 0.3 mg/kg. MEDI3726 had nonlinear PK with a short t1/2 (0.3–2 d). Three pts (15.8%) at baseline and 6 (33.3%) post-baseline had antidrug antibodies, with no correlation to PK exposure. Composite response rate across all doses was 2/33 (6.1%). Time to response was 0.3 mo; duration of response was 1.8–3.8 mo. Median progression-free survival was 3.9 mo and median overall survival was 10.6 mo. Conclusions: An MTD was not identified, but drug-related AEs (skin toxicities and effusions) prevented raising the dose over 0.3 mg/kg and limited the number of cycles. Responses were seen at higher doses, but were not durable as pts discontinued due to drug-related AEs. Clinical trial information: NCT02991911.

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Phase II study of bevacizumab in combination with cisplatin and docetaxel as first-line treatment of patients (p) with metastatic non-squamous non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19023 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19023-e19023

Author(s):

N. Ferrer ◽

M. Cobo ◽

A. Paredes ◽

M. Méndez ◽

J. Muñoz-Langa ◽

...

Keyword(s):

Phase Ii ◽

Stage Iv ◽

Progression Free Survival ◽

Median Number ◽

Line Treatment ◽

Eligibility Criteria ◽

Platinum Based Chemotherapy ◽

History Of ◽

Grade 3 ◽

Number Of Cycles

e19023 Background: Bevacizumab (B), in addition to platinum-based chemotherapy, is indicated for 1st-line treatment of p with advanced NSCLC other than predominantly squamous cell histology. B has been shown to improve progression free survival (PFS) and overall survival (OS) when combined with cisplatin/gemcitabine and carboplatin/paclitaxel, respectively. However, there are limited data on the safety and efficacy of B in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open- labeled, single-stage phase II trial of cisplatin (C), docetaxel (D) and B for NSCLC. Methods: Eligibility criteria: chemo- naïve, stage IIIB wet or IV, non-squamous NSCLC, PS 0–1, no brain metastases and no history of gross hemoptysis. P received D (75 mg/m2), C (75 mg/m2), and B (15 mg/kg iv) on day 1 every 3 weeks for up to 6 cycles, followed by B 15 mg/kg alone every 3 weeks until disease progression or toxicity. Primary endpoint: PFS. Results: 50 p were enrolled (enrollment completed): 24% female, median age 60 (36–74), PS 1: 64%, adenocarcinoma: 72%; stage IV: 92%. Two p did not start treatment. Median follow-up is 5.3 months (range 0–13.6). Median number of cycles of B was 7 (range 0–18). 56% completed 6 cycles of treatment; 24% received ≥ 12 cycles of B. Most frequent grade ≥ 3 toxicities: diarrhea (14.6%), fatigue (14.6%), dyspnea (9.8%), anorexia (4.9%), alopecia (4.9%), esophagitis (4.9%), constipation (4.9%), mucositis (12.2%), proteinuria (4.9%); hematological toxicities: neutropenia (22%), febrile neutropenia (9.8%), leucopenia (14.6%), lymphopenia (4.9%). Of interest, 41.5% developed grade <3 epistaxis and 17% hypertension (1 p grade 3). One p died due to hemoptysis. 46 p were evaluable for response: 29 PRs (ORR: 63%). 18 of 48 p have experienced progression or death with a median SLP of 7.8 months (95% CI: 6.6-NR). Median OS is 13.5 months (95% CI: 12.7–13.6; 81.2% p censored); 1-year survival is 83.9% (95% CI: 67.4%-92.5%). Conclusions: Treatment with C, D and B, followed by maintenance B in 1st line of advanced non-squamous NSCLC shows an acceptable toxicity profile and promising efficacy. Final results will be presented. [Table: see text]

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Cisplatin and capecitabine with and without docetaxel as a first-line chemotherapy in patients with metastatic gastric carcinoma: Single clinical experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15194 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15194-e15194

Author(s):

Mekhty Narimanov ◽

Alexey Tryakin ◽

Varlam Zarkua ◽

Igor Bazin ◽

August Garin ◽

...

Keyword(s):

Gastric Carcinoma ◽

Median Overall Survival ◽

Progression Free Survival ◽

Primary Prophylaxis ◽

Median Number ◽

First Line ◽

Free Survival ◽

Grade 3 ◽

Number Of Cycles ◽

Line Chemotherapy

e15194 Background: Cisplatin and capecitabine and docetaxel are active agents for treatment of metastatic gastric carcinoma. We underwent analysis of efficacy and toxicity of douplet (CX ) and triplet (DCX) regimens which were used in our department as a first-line chemotherapy in patients with metastatic gastric carcinoma. Methods: Pts with metastatic gastric carcinoma were nonrandomly allocated to DCX regimen (docetaxel 75 mg/m2 i.v. day 1, cisplatin 75 mg/m2 i.v. day 1, capecitabine 1650 mg/m2 per os days 1-14) or CX regimen (cisplatin 75 mg/m2 i.v. day 1, capecitabine 2000 mg/m2 per os days 1-14 ). Up to 6 cycles were provided every 3 weeks. G-CSF was not routinely used for primary prophylaxis. Results: From 2008 to 2012 81 pts were included in the study (DCX – 37 pts, CX – 44 pts). Pts characteristics were similar in both groups (table 1). Median number of cycles in both groups was 5 (range, 1-6). Grade 3-4 toxicity (per cycle) in DCX and CX groups were neutropenia 24,9% and 16,1%, deep venous thrombosis – 2% and 0%, diarrhea – 6.2% and 7,4%, stomatitis – 3.8% and 2,2%, infection – 11% and 0%, anemia 14% and 13,5% pts, respectively. No toxic deaths were observed. Median progression-free survival (PFS) in DCX and CX were 7,5 months (95% CI 6,1-8,9) and 5,4 months (95% CI 5,0-6,2; p=0.0009), median overall survival (OS) 14,5 months (95% CI 10,1-18,9) and 9,3 months (95% CI 9,2-10,2; p=0.0018), respectively. Conclusions: Addition of docetaxel to the combination of cisplatin and capecitabine associates with significant improvement of PFS and OS. Higher rate of infection requires use of G-CSF in primary prophylaxis. [Table: see text]

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FOLFIRINOX in pancreatic cancer patients age 75 years or older.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.362 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 362-362 ◽

Cited By ~ 1

Author(s):

Jonathan Mizrahi ◽

Jane Rogers ◽

Kenneth R. Hess ◽

Robert A. Wolff ◽

Gauri Rajani Varadhachary ◽

...

Keyword(s):

Pancreatic Cancer ◽

Progression Free Survival ◽

Standard Of Care ◽

Initial Study ◽

Similar Efficacy ◽

Median Number ◽

Hematologic Toxicity ◽

Grade 3 ◽

Md Anderson ◽

Number Of Cycles

362 Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS) (11.1 vs 6.8 months [m] with gemcitabine, P < 0.001), pts > 75 yrs old were excluded from this study. As per SEER 2011-2015 data, 38% of new PC cases are diagnosed in pts age > 75. The purpose of this study was to assess the safety and efficacy of FOLFIRINOX in this group of pts. Methods: We retrospectively analyzed unresectable PC pts, age ≥ 75, treated with FOLFIRINOX at MD Anderson since 2011. Data obtained include demographics, line of treatment (tx), starting dose, progression free survival (PFS), OS and toxicities. Response was determined by chart documentation. Primary outcomes were mOS and rates of grade 3/4 hematologic toxicity (HT). Results: A total of 24 pts (19 male) were included with median age of 76 (range 75 to 84). 18 had metastatic disease, and FOLFIRINOX was the 1st line of tx for 18 of the 24 pts. The median number of cycles administered was 4 (range 1 to 12). The most frequent starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m2, respectively. Bolus 5-FU and leucovorin were omitted in all but 3 pts. Median PFS was 3.7 m (95% CI: 3.0-5.7) with mOS of 11.6 m (95% CI: 6.14-15.7). 16 pts (67%) experienced disease control (response to tx or stable disease). Grade 3 or 4 HT occurred in 11 pts (46%), and 9 (38%) were supported with granulocyte colony-stimulating factor at some point during tx. 6 pts (25%) required hospital admission for any toxicity, most commonly infection (3 pts), and 10 (42%) stopped FOLFIRINOX due to toxicity, most commonly fatigue (6 pts). Conclusions: In this single-center retrospective analysis of 24 unresectable PC pts age 75 or older given FOLFIRINOX, OS outcomes were similar to those reported by Conroy et al in the original trial which excluded pts older than 75. In our review, toxicities including incidences of grade 3 or 4 HT were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar efficacy and toxicity when compared to younger pts.

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Cisplatin, Fluorouracil in Bolus Injection, and Leucovorin in First-Line Therapy for Advanced Gastric Cancer as an Alternative to Protocols With Infusional Fluorouracil

Journal of Global Oncology ◽

10.1200/jgo.18.00176 ◽

2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Rafael C. Coelho ◽

Pedro D.P. Abreu ◽

Mariana R. Monteiro ◽

Ana Paula Stramosk ◽

Alvaro Henrique I. Garces ◽

...

Keyword(s):

Gastric Cancer ◽

Progression Free Survival ◽

Median Number ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Grade 3 ◽

Number Of Cycles ◽

Line Setting ◽

Platinum Agents

PURPOSE Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide. Platinum agents and fluoropyrimidines are the main compounds used in the first-line setting for advanced GC. Given the activity of fluorouracil (FU) bolus, the PFL protocol, a chemotherapy regimen combining cisplatin, FU bolus, and leucovorin, was incorporated at the Brazilian National Cancer Institute, because this schedule does not require hospitalization or infusion pumps. This study aims to evaluate the outcomes of PFL in the first-line setting for patients with advanced GC. MATERIALS AND METHODS This was a retrospective cohort study evaluating patients with advanced GC treated in the first-line setting with cisplatin 80 mg/m2 on day 1 and FU bolus 400 mg/m2 plus leucovorin 20 mg/m2 on days 1, 8, 15, and 22 every 4 weeks, from January 2008 to December 2014. RESULTS A total of 109 patients were enrolled. The median number of cycles received per patient was four (one to 11). Complete responses were achieved in 6.4% and partial responses in 14.7%. Median progression-free survival was 6.3 months (95% CI, 5.08 to 7.58 months) and median overall survival was 8.3 months (95% CI, 6.79 to 9.87 months). Thirty-four (31.2%) patients were alive in 1 year. Grade 3 and 4 adverse events were experienced by 26.6% and 3.7% of patients, respectively, with dose reduction necessary in 9.1%. CONCLUSION PFL is active in advanced GC and could be an alternative for FU continuous infusion protocols in institutions with limited resources and/or low budget, which is the reality in many nations all over the world.

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Gemcitabine, cisplatin and methylprednisolone (GEM-P) in patients with T-cell lymphoma: Results from The Royal Marsden Hospital

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17507 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17507-17507

Author(s):

H. Arkenau ◽

M. Trumper ◽

B. Sirohi ◽

G. Chong ◽

I. Chau ◽

...

Keyword(s):

T Cell ◽

Progression Free Survival ◽

Median Number ◽

High Dose Chemotherapy ◽

High Dose ◽

Neutropenic Sepsis ◽

Royal Marsden Hospital ◽

Previously Treated ◽

Grade 3 ◽

Number Of Cycles

17507 Background: There is a need for novel, effective therapies for T-cell non-Hodgkin’s lymphoma (NHL). The combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) has shown activity in patients (pts) with relapsed Hodgkin’s disease and NHL (Chau I et al. Br J Haematol 2003, Baetz T et al. Ann Oncol 2003). We report a single institution retrospective analysis of GEM-P for pts with T-cell NHL. Methods: Sixteen pts with T-cell NHL treated at the Royal Marsden Hospital between June 2001 and March 2005 with GEM-P (gemcitabine 1 g/m2 D1, 8, 15; cisplatin 100 mg/m2 D15; methylprednisolone 1 g D1–5, repeated every 28D) were identified. Results: 16 pts (9 males and 7 females) were analysed. Histological subtypes were: angioimmunoblastic (n = 5), T-cell enteropathy (n = 2), NK/T cell nasal-type (n = 2), T-cell anaplastic (n = 3) and peripheral T-cell unspecified (n = 3). Median age was 55 years (range: 18–71 years), 69% had IPI-score ≥ 2 and 69% had stage III/IV disease. 15 /16 pts were pre-treated: median number of prior treatments: 1 (range: 0–4). At the start of GEM-P treatment pts presented with: primary refractory disease (n = 3), 1st relapse (n = 6), 1st relapse refractory (n = 3), 2nd relapse (n = 2) and 4th relapse (n = 1). Median time from diagnosis of T-cell NHL to start of GEM-P was 8.9 months(m) and median number of cycles given was 3 (range: 1–6). Of 16 evaluable patients, 3 pts (19 %) achieved complete remission (CR), 8 pts (50 %) achieved partial remission (PR), (ORR= 69%; CI-95% 41.4–89.0) and 5 pts (31%) progressed while on GEM-P. One pt received high dose chemotherapy (melphalan/etoposide) after CR to GEM-P. After a median follow up of 17.4m the mean progression free survival (PFS) was 9m (range 1.15–37.5). The median overall survival (OS) has not been reached and the survival probability at 1 year was 68.2% (95% CI: 40–85). The main grade 3/4 toxicities were myelosuppression (leucopenia 62%, neutropenia 62% and anaemia 12%) and required granulocyte colony stimulating factor (GCSF) in 3 pts with neutropenic sepsis and in 1 pt with neutropenia. Conclusion: GEM-P has encouraging efficacy with an acceptable toxicity profile in pts with previously treated T-cell NHL. [Table: see text]

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Subcutaneous omacetaxine mepesuccinate in imatinib-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation: Data from an ongoing phase II/III trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7008 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7008-7008

Author(s):

J. E. Cortes ◽

H. J. Khoury ◽

S. Corm ◽

F. Nicolini ◽

T. Schenk ◽

...

Keyword(s):

Tyrosine Kinase ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Median Number ◽

Clinical Activity ◽

Imatinib Resistant ◽

T315i Mutation ◽

Grade 3 ◽

Induction Cycle ◽

Number Of Cycles

7008 Background: Omacetaxine (OM), a first-in-class cetaxine shows clinical activity against Ph+ CML with a mechanism independent of tyrosine kinase inhibition. Currently available tyrosine kinase inhibitors (TKIs) have no activity against T315I. Methods: Adult Pts with T315I+ CML following TKI failure received OM induction at 1.25 mg/m2 subcutaneous (SC) twice daily (BID) for 14 days every 28 days followed by maintenance at 1.25 mg/m2 SC BID for 7 days every 28 days (maintenance after at least one induction cycle and achievement of hematologic response). Results: 66 pts (39 chronic [CP], 16 accelerated [AP] and 11 blast phase [BP]) have been enrolled. All had failed prior imatinib and 80% failed ≥2 prior TKIs. Median age is 58 yrs. Median disease duration is 58 mos. OM is well tolerated with transient myelosuppression as the primary toxicity. Grade 3/4 non-hematologic events are diarrhea (2%) and fatigue (4%). Efficacy data are available for 44 Pts. In CP Pts, the median number of cycles is 4 (1–22) with 39% having received ≥ 6 cycles of therapy; 64% of Pts have had the T315I clone reduced to below detection limits; the 2-year progression free survival is 70%. Conclusions: Omacetaxine in T315I+ CML Pts results in de-selection of the T315I clone and induces hematologic and cytogenetic responses. [Table: see text] [Table: see text]

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Results of the VENUS study: Bevacizumab efficacy and safety in platinum-sensitive recurrent ovarian cancer (OC)—A real-life ambispective study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5540 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5540-5540

Author(s):

Isabelle Laure Ray-Coquard ◽

Jerome Alexandre ◽

Francois Goldwasser ◽

Jean-Philippe Spano ◽

Dominique Berton-Rigaud ◽

...

Keyword(s):

De Novo ◽

Real Life ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Free Survival ◽

Life Study ◽

Platinum Sensitive ◽

Real Life Setting ◽

Grade 3

5540 Background: The VENUS study reports on the efficacy/safety of bevacizumab (Bev) in patients (pts) treated in the real-life setting. Methods: In this multicentric observational ambispective VENUS study, all Pts were naive of any antiVEGF and received Bev +/- chemotherapy. Pts were followed until progression or death, for a maximum of 3 years since Bev initiation. De novo side effects were defined as symptoms for which patients were naïve at baseline. Results: 148 OC pts were included (27 centres), 10 excluded and 8 were lost of follow-up. 52 were retrospective. Median age 64 years (55-70). 84.1% were advanced. Median duration of Bev was 8.6 months, min 1 max 36 months. Initial Bev dose was 15 mg/kg Q3W for 65.3%, 10.0 for 22.5%, 7.5 for 10.2% and 5.0 for 2%. 2 pts presented with thrombotic micro-angiopathy (1.4%). Before Bev, hypertension (HTN) was present in 28.9%; proteinuria in 11.3%. Incidence of de novo HTN was 25%. 43 pts (31.2%) experienced de novo Grade 1-2 Pu, for a total of 56 events, no grade 3-4 was observed. A total of 12 Grade 4 events occurred: 9 neutropenia and 3 thrombopenia. Mean overall survival (OS) and progression free survival (PFS) were 30.0 and 13.3 months, respectively. Conclusions: 1) 1/3 of pts were treated at low doses in this real-life study; 2) safety of Bev in real-life was manageable and as expected, 3) OS and PFS were consistent with those reported in the OCEANS study: PFS 12.4 and OS 33.6 months but lower than in the GOG-0213 study: PFS 13.8 and OS 42.6 months. De novo events recorded during follow-up. [Table: see text]

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Bevacizumab (B), cisplatin, and vinorelbine in chemotherapy-naive patients (p) with nonsquamous non-small cell lung cancer (NSCLC): A Galician Lung Cancer Group phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19089 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19089-e19089

Author(s):

L. Leon ◽

S. Vázquez ◽

J. M. Gracia ◽

M. Lázaro ◽

J. L. Fírvida ◽

...

Keyword(s):

Lung Cancer ◽

Phase Ii ◽

Survival Data ◽

Safety Profile ◽

Progression Free Survival ◽

Median Number ◽

Stage Iiib ◽

Eligibility Criteria ◽

Grade 3 ◽

Number Of Cycles

e19089 Background: Bevacizumab, an anti-VEGF monoclonal antibody, improves response rates and prolongs survival in p with non squamous NSCLC when combined with carboplatin-paclitaxel or cisplatin-gemcitabine. This single-arm, open-labeled phase II trial aims to evaluate the efficacy and safety profile of B in combination with another widely used chemotherapy doublet for NSCLC: cisplatin and vinorelbine. Methods: Chemotherapy-naïve p diagnosed with stage IIIB or IV non squamous NSCLC received cisplatin (80 mg/m2), vinorelbine (25 mg/m2 IV days 1 and 8) and B (15 mg/kg IV) on day 1 every 3 weeks for up to 6 cycles followed by B 15 mg/kg alone every 3 weeks until disease progression. Main eligibility criteria were: PS 0–1, no brain metastases, no history of hemoptysis, stable cardiac condition and no full dose anticoagulation. Primary endpoint was progression-free survival and secondary endpoints were RR, duration of response, OS, 1-year survival and safety profile of the combination. Results: 38 p have been enrolled in the study and data of 27 p have been included in this analysis. P characteristics were: male 66.7%; median age 57 years (range 41–74); ECOG PS 0/1 (%) 33.3/66.7; adenocarcinoma/other (%) 74.1/25.9; stage IIIB/IV (%) 25.9/74.1. Median number of cycles for B/cisplatin/vinorelbine was 4.0 (range 1–6) and median number of cycles for B maintenance was 2 (range 1–4). 17 p were evaluable for response according to RECIST criteria: PR 29.4% and SD 41.2%. With a median follow-up of 3.9 months (range 0.7–11.1), median PFS was 4.6 months (95% CI: 2.6–6.6) and median OS has not been reached yet. Hematological toxicities were: 1 p gr. 3 anemia; 2 p gr. 3 and 2 p gr. 4 leucopenia; 10 p gr. 3, 1 p gr. 4 neutropenia and 3 p febrile neutropenia. Most common grade 3/4 non hematological toxicities were: vomiting (1p gr. 4), high blood pressure, asthenia and hyperglycemia. 1 p experienced gr. 4 abdominal pain, 1 p. gr. 4 constipation, 1 p. gr. 4 nausea and 1 p gr. 4 respiratory infection. No grade 3/4 hemoptysis were reported. Conclusions: This interim analysis shows that B in combination with cisplatin and vinorelbine is safe and well tolerated and has a promising activity in chemo-naïve p with non squamous NSCLC. Survival data will be updated. [Table: see text]

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