Activity of new agents (NAs) as third-line treatment in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) after a long-term disease control (LTDC) with abiraterone acetate (AA) or enzalutamide (ENZ) post docetaxel (DOC): Preliminary results from a multicenter Italian study.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 325-325
Author(s):  
Antonello Veccia ◽  
Ugo De Giorgi ◽  
Gaetano Facchini ◽  
Lucia Fratino ◽  
Donatello Gasparro ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Consecutive Series ◽  
Line Treatment ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Progression Of Disease ◽  
Third Line ◽  
Third Line Treatment

325 Background: Although the expected median progression free survival (mPFS) with AA and ENZ in DOC-pretreated pts is 6-8 mos, a quote of pts may experience a LTDC without progression of disease (PD) for more than 12 mos. Since the androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, some mechanisms of resistance could be common to all NAs. This may be crucial in planning their sequential use, mainly when a LTDC is observed in hormone NAs-based (HNAs) second line. The present study was aimed to assess the activity of NAs in pts who previously showed a LTDC with HNAs administered after DOC. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. For the study purpose, LTDC was defined as the absence of PD ≥ 12 mos in pts treated with second-line AA or ENZ. Results: A consecutive series of 291 mCRPC pts, median age 71 yrs (46-91), with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received NAs as second line after DOC: in particular 160 (55%) received AA and 32 (11%) ENZ, with 41 pts (21%) showing a LTDC (36 AA – 5 ENZ). Among LTDC pts, third line treatment was cabazitaxel (CABA) in 25 cases and one hormonal NA in the remaining (2 AA - 14 ENZ). The clinical outcomes of the third line therapy are detailed in the table. Conclusions: From this preliminary data, it appears that third line CABA could be slightly more active in pts achieving a LTDC with HNAs in second line LTDC, despite the clinical outcomes were not significantly different compared to HNAs. Analyses on larger patients populations are needed to confirm these findings. [Table: see text]

Activity of new agents (NAs) as third-line treatment in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) showing a primary resistance (PRes) to NAs-based second line therapy after docetaxel (DOC): Preliminary results from a multicenter Italian study.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 216-216
Author(s):  
Orazio Caffo ◽  
Ugo De Giorgi ◽  
Gaetano Facchini ◽  
Lucia Fratino ◽  
Donatello Gasparro ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Objective Response ◽  
Progression Free Survival ◽  
Consecutive Series ◽  
Line Treatment ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Primary Resistance ◽  
Third Line ◽  
Third Line Treatment

216 Background: The androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, abiraterone acetate (AA), cabazitaxel (CAB), and enzalutamide (ENZ). It is postulated that some mechanisms of resistance may be common to all NAs. This may be crucial in planning their sequential use, mainly when a PRes to one of them is observed. The present study assessed the activity of NAs in pts who previously experienced a PRes to another NA administered after DOC. Methods: We collected data of pts who received sequentially two NAs after DOC in 32 Italian hospital. For each pt we recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we consider with PRes all pts progressing within 3 months after second line NA start. All other pts were considered as without PRes. Results: A consecutive series of 271 mCRPC pts, median age 71 yrs (46-91), with bone (89%), nodal (56%) or visceral (19%) mets, was collected. All pts received NAs as second line after DOC (AA 54% – CAB 34%– ENZ 12%) and 54 (20%) showed a PRes. Among these, third line treatment [AA (31%), CAB (42%), and ENZ (27%)], produced a biochemical and an objective response rate of 11% in both cases, with a median progression free survival (PFS) and a median overall survival (OS) of 4 mos and 8 mos, respectively. No statistically significant differences were observed in terms of clinical outcomes on the basis of NA sequences (see Table). Conclusions: It appears from this preliminary data, that the activity of NAs in pts showing a PRes to second line NAs is very limited, regardless the NA is administered. [Table: see text]

Sequential administration of new agents (NAs) after docetaxel (DOC) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts): Impact of disease control (DC) duration in second line on the subsequent line outcomes.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 210-210
Author(s):  
Francesca Maines ◽  
Ugo De Giorgi ◽  
Gaetano Facchini ◽  
Lucia Fratino ◽  
Donatello Gasparro ◽  
...  
Keyword(s):  
Disease Control ◽  
Clinical Outcomes ◽  
Abiraterone Acetate ◽  
Consecutive Series ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Primary Resistance ◽  
Sequential Administration ◽  
Progression Of Disease ◽  
Third Line

210 Background: Abiraterone acetate (AA), cabazitaxel (CABA), and enzalutamide (ENZ) are NAs which demonstrated their efficacy in mCRPC pts who have previously treated with DOC. Unfortunately all pts develop a resistance to these drugs and eventually show a progression of disease. Since the androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, some mechanisms of resistance could be common to all NAs. To date, NAs are sequentially administered in the hope of obtaining a cumulative survival benefit. To date it is unknown if the DC duration influence the outcomes of the subsequent treatments. The present study was aimed to retrospectively assess this issue in a large series of mCRPC pts. Methods: We recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we categorized the pts according to the duration of DC (absence of progression) during NA-based second line: DC ≤ 3 mos (primary resistance – PRe); DC from 3.1 to 11.9 mos (intermediate sensitivity – IS); DC ≥ 12 mos (long term disease control – LTDC). Results: A consecutive series of 291 mCRPC pts, median age 71 yrs (46-91), with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received a NA-based as second line after DOC: 160 (55%) received AA, 99 (33%) CABA and 32 (11%) ENZ. PRe was observed in 56 pts (23 AA – 25 CABA – 8 ENZ), IS in 178 (101 AA – 58 CABA – 19 ENZ), LTDC in 57 (36 AA – 16 CABA – 5 ENZ). The third-line clinical outcomes are detailed in the table. Conclusions: From this data, it appears that DC duration may be a prognostic factor, as a probable result of pts/disease selection. In fact, pts progressing more than 12 mos from the start of NA-based second line appear to have more probabilities to live longer, compared to pts progressing earlier, when they receive another NA-based third line therapy. [Table: see text]

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in metastatic castration-resistant prostate cancer (mCRPC) pts receiving a new agent (NA)-based third line treatment: Preliminary results from a multicenter Italian study.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 211-211
Author(s):  
Orazio Caffo ◽  
Ugo De Giorgi ◽  
Daniele Alesini ◽  
Lucia Fratino ◽  
Cinzia Ortega ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Prognostic Value ◽  
Cox Regression ◽  
Objective Response ◽  
Consecutive Series ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Third Line ◽  
Third Line Treatment

211 Background: The NLR is a marker of systemic inflammatory response: several studies investigated its prognostic relevance in mCRPC but to date no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcome and NLR in a large series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 291 mCRPC pts with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received a NA-based third line: 90 received AA, 123 CABA and 78 ENZ. At the time of this analysis, data on NLR were available for 198 pts (68%): AA 68 (75%) – CABA 80 (65%) – ENZ 50 (64%): the median value was 3.1 (IQR 2.2-4.7). In the univariate analyses, the NLR as a discrete variable using the median value of 3.1 as threshold, was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001 and p = 0.001, respectively). No association was observed with either biochemical or objective response. These results were confirmed at the multivariate analysis. In Kaplan-Meier analysis, the median OS from the start of third-line was higher (18.2 vs 8.1 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 6.3 and 3.5 in pts with NLR ≤ 3.1 and > 3.1, respectively. Conclusions: At the best of our knowledge, this is the first report on the NLR value in mCRPC third line treatment. From our preliminary data, it appears that NLR may be a prognostic and predictive factor in mCRPC pts, treated with NA-based third line.

Is metronomic cyclophosphamide (mCTX) a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) in the era of new agents (NAs)? A retrospective multicenter Italian study.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 326-326
Author(s):  
Orazio Caffo ◽  
Ugo De Giorgi ◽  
Francesco Ferraú ◽  
Maddalena Donini ◽  
Gaetano Facchini ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Outcomes ◽  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
Grade 3 ◽  
Clinical Records

326 Background: Several NAs, such as abiraterone acetate (AA), cabazitaxel (CABA), and enzalutamide (ENZ), are able to significantly prolong mCRPC pts survival after docetaxel (DOC) failure. Nevertheless, all pts eventually show progressive disease with NAs and several pts may require further treatment. mCTX was considered as a feasible and tolerable therapeutic option after DOC failure before the introduction of NAs in the clinical practice. The present retrospective study describes the clinical outcomes of mCTX, used in mCRPC pts after the failure of both DOC and at least one NA. Methods: We retrospectively reviewed the clinical records of all mCRPC pts treated in 8 Italian hospitals after the introduction of NAs in the clinical practice. We considered as eligible for the present analysis all pts who received mCTX after DOC and at least one NA. All pts were treated with CTX 50 mg po daily until disease progression. Results: From December 2011 to June 2015, a consecutive series of 48 mCRPC pts, median age 72 yrs (56-90), with bone (94%), nodal (67%) or visceral (25%) mets, was treated with mCTX. All pts have previously received a DOC-based chemotherapy followed by only one NA in 21 cases, two NAs in 20, and all three NAs in 7. The median duration of the treatment was 10.4 wks (range 3.6-61.1). Recorded grade 3-4 toxicities were: anemia (5 pts), leucopenia (1), thrombocytopenia (2), fatigue (2), and anorexia (1). Seven pts (14%) achieved a PSA reduction ≥ 50% and 2 (4%) an objective response. The median progression free survival (PFS) was 3.5 mos with 7 pts (14%) showing a PFS ≥ 9 mos. The median overall survival was 6.9 mos. Conclusions: In our experience, mCTX was a feasible and well tolerated therapeutic option in heavily pre-treated pts with very advanced mCRPC. Despite its activity was limited, the clinical outcomes of this cheap treatment are similar to those observed with NAs administered in third/fourth line with a quote of pts experiencing a prolonged disease control. Prospective studies are needed to define the therapeutic role of mCTX after NAs in mCRPC pts.

scholarly journals Cost Effectiveness Analysis of Eribulin Mesylate as a Treatment for Metastatic Breast Cancer in Spain: Management in the Later Line of Therapy

10.36469/9834 ◽  
2015 ◽  
Vol 3 (2) ◽  
pp. 180-193
Author(s):  
Gabriel Tremblay ◽  
Unnati Majethia ◽  
Ilias Kontoudis ◽  
Jesús De Rosendo
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cost Effectiveness ◽  
Metastatic Breast ◽  
Sensitivity Analyses ◽  
Line Treatment ◽  
Second Line ◽  
Life Years ◽  
Third Line ◽  
Third Line Treatment

Background: Two thirds (62%) of metastatic breast cancer (MBC) patients in Western Europe have human epidermal growth factor receptor 2 (HER2)-negative disease, for which anthracyclines and taxanes are recommended as first-line treatments, followed by microtubule-targeting agents such as capecitabine, vinorelbine and/or eribulin. The study objective was to compare the cost-effectiveness of eribulin in Spain as a second-line treatment for HER2-negative MBC with its current status as a third-line treatment for patients who have received capecitabine. Methods: A Markov model was developed from the perspective of the Spanish healthcare system. The model had three health states: Stable; Progression and Death. In Stable, patients received eribulin or: capecitabine and vinorelbine for HER2-negative patients; primary treatment of physician’s choice (TPC) for post-capecitabine patients. In Progression, all patients received secondary TPC. Model inputs were overall survival, progression-free survival and costs relating to chemotherapies, grade 3/4 adverse events and healthcare utilization. Sensitivity analyses were conducted to identify uncertainty. Results: As second-line treatment, Eribulin was associated with a greater incremental benefit in life years (LYs) and quality-adjusted life years (QALYs) than capecitabine and vinorelbine. Erubilin as third-line treatment was associated with greater benefit in life years (LYs) and QALYs than TPC. The incremental cost-effectiveness ratios (ICERs) for eribulin were higher in the second-line than the third-line setting in terms of LYs (€35,149 versus €24,884) and QALYs (€37,152 versus €35,484). In both settings, deterministic sensitivity analyses demonstrated that the ICER is most sensitive to the eribulin price. Conclusion: Eribulin is cost-effective as second-line treatment for HER2-negative MBC patients in Spain; albeit, slightly less so than as third-line treatment for MBC patients who have received capecitabine (an ICER per QALY difference of €1,668). This difference may fall within the margin of error for the model and could potentially be addressed by a minor reduction in the eribulin price.

Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Geoffroy Bilger ◽  
Anne-Claire Toffart ◽  
Marie Darasson ◽  
Michaël Duruisseaux ◽  
Lucie Ulmer ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Multicentric Study ◽  
Significant Difference ◽  
Third Line ◽  
And Performance ◽  
Line Setting

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.

scholarly journals P469 Stay in class or switch out of class after anti-TNF failure in inflammatory bowel disease (IBD). Real-world data from a large district general hospital

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S414-S414
Author(s):  
H Johnson ◽  
S Vythilingam ◽  
S McLaughlin
Keyword(s):  
Clinical Remission ◽  
Disease Type ◽  
Line Treatment ◽  
Second Line ◽  
Real World Data ◽  
Effective Treatment Option ◽  
Significant Cost ◽  
Third Line ◽  
Biologic Drug ◽  
Third Line Treatment

Abstract Background Biosimilar infliximab (IFX) and adalimumab (ADA) are well-proven cost-effective anti-TNF drugs in IBD; in our practice, the majority of patients with IBD receive IFX or ADA first line. Since the introduction of Vedolizumab (VED) and Ustekinumab (UST) some have recommended switching out of class after failing a single anti-TNF. This practice has significant cost implications. To establish the outcome of treatment response in patients treated with a second anti-TNF agent after anti-TNF failure compared with the outcome of patients treated with VED and UST after anti-TNF failure. Methods We maintain a prospective IBD database. We searched our database for the outcomes of patients who failed their first anti-TNF drug but were in a clinical remission 6 months after changing to a second or third biologic drug. Disease type, age, gender and response to their second and third biologic drug were recorded. Clinical remission was defined as off steroids with calprotectin &lt;250 and no symptoms of active IBD. Results Two hundred and eighty-seven patients were identified. One hundred and forty (48.8%) were male. Mean age was 43.2 (range 18–94). Disease type was 75 (26%) UC, 210 (73.2%) CD, 2 (0.7%) IBD-U. One hundred and ninety-three patients received IFX 1st line, 118 (40%) failed. Of these 84 (72%) received ADA, 28 (24%) VED and 6 (5%) UST second line. Remission with second-line treatment was achieved in 58 (69%); ADA, 18 (64%); VED, 6 (100%); UST. Remission with third line treatment; was achieved in 6 (100%); VED; 5 (100%); UST. Ninety-four patients received ADA 1st line, 33 (35%) failed. Of these 11 (33%) received IFX, 10 (30%) VED and 8 (24%) UST second line. Remission with second-line treatment was achieved in 6 (55%); IFX, 10 (100%); VED and 8 (100%); UST. Remission with third line treatment; was achieved in 1 (100%); VED, 4 (100%); UST. Conclusion Our data suggest that treatment with ADA after IFX failure is an effective treatment option whereas IFX treatment after ADA failure is less effective. It is interesting that the majority of those who failed the anti-integrin treatment second line responded to third line ADA. These data are consistent with earlier anti-TNF studies including GAIN (Gauging Adalimumab efficacy in Infliximab Non-responders) and SWITCH (Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial) which demonstrated that anti-TNF failure is not a class effect. We recommend prescribing a second anti-TNF after anti-TNF failure in preference to using an anti-integrin second line. This practice will lead to significant cost savings for the health care economy.

scholarly journals HIV-1 Drug Resistance and Third-Line Therapy Outcomes in Patients Failing Second-Line Therapy in Zimbabwe

2018 ◽  
Vol 5 (2) ◽  
Author(s):  
Cleophas Chimbetete ◽  
David Katzenstein ◽  
Tinei Shamu ◽  
Adrian Spoerri ◽  
Janne Estill ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Line Treatment ◽  
Second Line ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Cd4 Cell Count ◽  
Line Therapy ◽  
Third Line ◽  
Cd4 Cell ◽  
Third Line Treatment

Abstract Objectives To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests &gt;1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir. Results Genotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3–5.1) and 2.6 years (IQR, 1.6–4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728–208 920 copies/mL) and 201 cells/mm3 (IQR, 49–333 cells/mm3). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age &gt;24 years (P = .003) and CD4 cell count &lt;200 cells/mm3 (P = .007). In multivariable analysis, only age &gt;24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69–13.38; P = .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months. Conclusions The prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.

A phase II study of enzastaurin as second- or third-line treatment of non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7543-7543 ◽  
Author(s):  
G. Bepler ◽  
Y. Oh ◽  
H. Burris ◽  
A. Cleverly ◽  
M. Lahn ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Line Treatment ◽  
Platinum Based Chemotherapy ◽  
Third Line ◽  
Third Line Treatment

7543 Background: Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKC and the PI3K/AKT pathway, induces tumor cell apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. Over-expression and activity of PKC and PI3K/AKT are associated with poor prognosis and treatment resistance in NSCLC. This multicenter phase II trial of enzastaurin as second- and third-line treatment of NSCLC determined the rate of progression-free survival (PFS) at 6 months (mos). Secondary objectives included safety and the rate of overall survival (OS) at 12 mos. Methods: Eligibility included metastatic (stage IV and wet IIIB) NSCLC and prior platinum-based chemotherapy. Patients (pts) received 500 mg of oral enzastaurin, once daily, until disease progression or unacceptable toxicity occurred. All pts were eligible for 2nd or 3rd line treatment. Results: In the 54 pts enrolled [54% M, 46% F; median age: 63 (range: 43–82); 22.2% stage III, 77.8% stage IV, ECOG PS=2], adenocarcinoma was the most frequent diagnosis (67%). Prior therapies included radiotherapy (74%) and EGFR inhibitors (28%). At the final analysis, the median PFS was 1.9 mos (95% CI: 1.7–1.9), and the PFS rate at 6 mos was 14% (95% CI: 4.4%–23.6%). The median OS was 9.9 mos (95% CI: 6.5–14.6). The OS rate at 12 mos was 46.3% (95% CI: 32.1%–60.5%). Nineteen pts (35%) had stable disease (SD); none had a complete or partial response. Ten (19%) pts were on-study for =6 cycles, 3 of whom continued for >10 months. The most common toxicity, fatigue (grade =2, n=15), occurred within 1 week of enrollment and was not reported in pts with SD. Grade =3 toxicities observed were ataxia (n=1), fatigue (n=2), thrombo-embolism (n=1), and anemia (n=1). Two pts discontinued due to fatigue and dizziness. Five pts died on-study and 4 within 30 days of discontinuation due to PD. Post-study chemotherapy (n=28) included bevacizumab, erlotinib, pemetrexed, gemcitabine, cisplatinum and paclitaxel. Conclusion: Although no objective tumor responses occurred, 14% of the pts were progression-free at 6 months. Based on encouraging survival and tolerability data, further evaluation of enzastaurin as a single agent or in combination, is warranted in NSCLC. No significant financial relationships to disclose.

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