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.

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)

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]

A phase II study of irinotecan as single agent in the third-line treatment of unresectable or metastatic gastric cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16084-e16084 ◽  
Author(s):  
Zhe Zhang ◽  
Zhiyu Chen ◽  
Xiaodong Zhu ◽  
Xiaowei Zhang ◽  
Xiaoying Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Metastatic Gastric Cancer ◽  
Line Treatment ◽  
The Third ◽  
Third Line ◽  
Third Line Treatment

Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8028-8028
Author(s):  
R. Jotte ◽  
P. Conkling ◽  
C. Reynolds ◽  
L. Klein ◽  
J. F. Fitzgibbons ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2nd-line ED-SCLC sensitive to 1st-line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1st-line platinum-based chemotherapy (recurrence or progression ≥90 days from 1st-line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m2/d (d, 1–3) or IV topotecan 1.5 mg/m2/d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p<0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2nd-line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]

Randomized multicenter phase II trial evaluating the sequencing of PD-1 inhibition with pembrolizumab (P) and standard platinum-based chemotherapy (C) in patients (pts) with metastatic non-small cell lung cancer (NSCLC) (AFT-09).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9088-9088
Author(s):  
Thomas A. Hensing ◽  
Xiaofei F. Wang ◽  
Junheng Gao ◽  
Tom Stinchcombe ◽  
Michael V. Knopp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cox Regression ◽  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cox Regression Analysis ◽  
Recist 1.1 ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

9088 Background: KEYNOTE-024 established single-agent P as a 1st-line option for pts with metastatic NSCLC without targetable alterations and PD-L1 tumor proportion score (TPS) ≥ 50%. KEYNOTE-189 and 407 established concurrent C + P as a treatment option irrespective of PD-L1 expression. In this randomized phase II selection trial, we explored sequencing of C and P in this pt. population. Methods: Eligible pts were randomized 1:1 to (arm A) C (carboplatin (AUC 6) + pemetrexed 500 mg/m2 (non-squamous) or paclitaxel 200 mg/m2 (squamous)) x 4 cycles followed by P 200 mg x 4 cycles, or the reverse sequence (arm B) of P x 4 cycles followed by C x 4 cycles. After 8 cycles, pts on both arms were eligible to receive maintenance P for up to 24 months. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review. Secondary endpoints included progression free survival (PFS) per RECIST 1.1 and overall survival (OS). Efficacy endpoints were also evaluated by PD-L1 expression. Results: 89 pts (47 arm B & 42 arm A) were enrolled and are included in the analysis (PD-L1 TPS 0/1-49%/≥50% = 24 pts (34%)/25 pts (36%)/21 pts (30%)). There was no significant difference in ORR (36% vs 38%, p = 0.829), median PFS (2.7 vs 5.5 months (mo), HR 1.25, 95% CI 0.77-2.02, p = 0.363) or OS (13.1 vs 19.8 mo, HR 1.25, 95% CI 0.69-2.25, p = 0.4573), arm B (Px4→C) vs arm A (Cx4→P). Multivariable Cox regression analysis demonstrated significant interaction between treatment and PD-L1 TPS ( < 50% vs ≥ 50%) for PFS (HR 6.76, 95% CI 2.14-21.35, p = 0.0011) and a trend for OS (HR 5.02, 95% CI 0.92-27.55, p = 0.0632), arm B vs arm A. Incidence of grade ≥3 adverse events was 71% for arm A and 65% for arm B. No new safety signals were observed. Conclusions: In pts with stage IV NSCLC and PD-L1 TPS ≥ 50% there was an observed improvement in PFS and OS in favor of C followed by P vs P x 4 followed by C. Given small # of pts and trial design, this observation should be considered hypothesis-generating, but supports further exploration of sequential C + P in this setting. Support:Merck Sharp & Dohme Corp.; https://acknowledgments.alliancefound.org Clinical trial information: NCT02591615.

Anlotinib combined with s-1 in the third-line or later-line treatment of stage IV non-small cell lung cancer: Study for phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21115-e21115
Author(s):  
Xiyue Yang ◽  
Xiaobo Du
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
Free Survival ◽  
The Third ◽  
Third Line ◽  
Third Line Treatment

e21115 Background: At present, for stage IV non-small-cell lung cancer (NSCLC), after the failure of second-line treatment, the effective rate of third-line treatment is not very well. We designed this study to evaluate the efficacy and safety of anlotinib combined with S-1 as a third-line treatment for patients with stage IV NSCLC. Methods: According to the inclusion and exclusion criteria, 29 patients will be treated with anlotinib plus S-1 based on Simon’s optimal two-stage design.They will undergo computed tomography (CT) every two cycles to assess the therapeutic effect according to RECIST.If the efficacy is assessed as SD, PR, CR after six cycles, anlotinib will be maintained until disease progression or death. Statistical analysis of the data will be conducted using SPSS (version 22.0).The primary endpoint is the objective response rate (ORR). The secondary endpoints are disease control rate(DCR),progression-free survival(PFS), overall survival(OS), and safety. Results: Between Jan 10, 2019, and Oct 31, 2020, a total of 29 patients were enrolled for treatment.At data cutoff (Jan 11, 2021),27(93.1%) patients had discontinued the study, and 2 (6.9%) patients were still receiving treatment. The median follow-up time was 11.2 months (IQR 8.2-20.1). Objective responses were achieved in 11 (37.9%; 95%CI 20.7-57.7) of 29 patients in the intention-to-treat population,which reached this trial’s primary endpoint. Disease control was achieved in 18 patients (62.1%; 95%CI 42.3-79.3);The median overall survival was 16.7months (95%CI 14.9-18.6);the median progression-free survival was 5.8 months (95% CI 2.9-8.7). The most common grade 3 adverse events were Gastrointestinal reactions (3[10.3%]),Fatigue (2[6.9%]), and Hypertension (2 [6.9%]).No grade 4 treatment-related adverse events, or treatment-related deaths occurred. Conclusions: The combination of anlotinib with S-1 in the third-line or later-line treatment of stage IV NSCLC shows promising anti-tumour activity and manageable toxicities in patients with NSCLC, and further study in phase 3 trials will be planned in the future. Clinical trial information: ChiCTR1900020948.

Response to selpercatinib versus prior systemic therapy in patients (pts) with RET fusion+ non-small-cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9032-9032
Author(s):  
Alexander E. Drilon ◽  
Oliver Gautschi ◽  
Benjamin Besse ◽  
Vivek Subbiah ◽  
Daniel Shao-Weng Tan ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Survival Duration ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Systemic Therapies

9032 Background: Selpercatinib, a first-in-class highly selective, potent, CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ lung or thyroid cancers. Selpercatinib demonstrated durable antitumor activity in previously treated pts with RET fusion+ NSCLC in an ongoing Phase 1/2 trial, LIBRETTO-001 (Besse et al., ASCO 2021). Methods: Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128; 16 countries, 89 sites). Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, duration of response, and safety. This post-hoc intrapatient analysis was based on a 30 March 2020 data cutoff date. Historical physician-reported best overall response (BOR) from last systemic therapy received prior to enrollment was compared with selpercatinib BOR by independent review committee per RECIST v1.1, with each patient serving as his/her own control. Results: In efficacy-evaluable pts (N = 218) who previously received platinum-based chemotherapy (chemo), median pt age was 61 years, the majority with ECOG of 0/1 (37%/61%), with a median of 2 (range: 1-15) prior systemic therapies. Overall, 57% of patients responded to selpercatinib while 16% responded to the immediate prior therapy. ORR improvements with selpercatinib were observed regardless of prior therapy: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%), or chemotherapy (58% vs 15%). A total of 108 patients (49%) did not respond to immediate prior therapy but responded to selpercatinib. Fewer patients had progressive disease as their BOR with selpercatinib (2%) compared to the immediate prior therapy (28%). The median duration of therapy for selpercatinib was notably extended compared with that of the immediate prior therapy (11.8 vs. 3.4 months, respectively). Conclusions: In pts with RET fusion+ NSCLC treated on LIBRETTO-001, systemic therapies administered prior to enrollment achieved less meaningful clinical benefit than selpercatinib. Selpercatinib demonstrated consistent efficacy regardless of the type of prior therapy. Clinical trial information: NCT03157128.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

Amrubicin as second- or third-line treatment for patients with HER2-negative metastatic breast cancer (MBC): A phase II trial of the Sarah Cannon Research Institute (SCRI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1086-1086
Author(s):  
John H. Barton ◽  
Eric Raefsky ◽  
William N. Harwin ◽  
Alejandro A. Inclan ◽  
Gerald Miletello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Phase Ii ◽  
Hematologic Toxicity ◽  
Significant Activity ◽  
Line Treatment ◽  
Prior Chemotherapy ◽  
Third Line ◽  
Grade 3 ◽  
Third Line Treatment

1086 Background: Anthracyclines demonstrate significant activity in breast cancer, but the potential for cardiotoxicity is dose-limiting. Amrubicin is a novel anthracycline with broad-spectrum preclinical activity and low potential for cardiotoxicity. We present phase II results from a phase I/II trial of amrubicin as second/third- line therapy for HER2- negative MBC. Methods: Women with measurable HER2-negative MBC with 1 or 2 prior chemotherapy regimens for metastatic disease and normal LVEF were eligible. Prior anthracycline- containing adjuvant therapy was allowed. Amrubicin 110 mg/ m2 IV every 3 weeks was administered until disease progression or intolerable toxicity. Tumor assessments were performed every 6 weeks and LVEF assessments every 12 weeks. The primary endpoint was progression free survival (PFS); a median PFS ≥ 4.5 months was considered a study result meriting further development of amrubicin. Results: 48 evaluable patients (pts) were treated from 1/2010 to 9/2011. Baseline characteristics included median age 57; 23% were triple-negative; 33% had 2 prior chemotherapy regimens for MBC; 38% had anthracycline- containing adjuvant therapy. Median treatment duration was 6 weeks (2 cycles), range 1- 12+ cycles. 8 pts (17%) had objective RECIST responses (1 CR, 7 PR); 5 of the 8 responders had received anthracycline-containing adjuvant therapy. 24 additional pts (50%) had stable disease at first reevaluation. The median PFS for all patients was 2.8 months (95% CI 1.6- 4.0 months); median PFS was similar for pts with 1 vs 2 previous regimens for MBC (95% CI 2.5 vs 4.0 months). 24% of pts were progression-free at 6 months. Neutropenia was the most common grade 3/4 toxicity (63%; 6% febrile neutropenia). No grade 3/4 non- hematologic toxicity occurred in > 5% pts. No cardiotoxicity occurred. Only 1 pt discontinued amrubicin due to toxicity (grade 2 fatigue). Conclusions: Amrubicin had good tolerability, no cardiotoxicity and was active as a second/third-line treatment for HER2- negative MBC, including pts previously treated with adjuvant anthracyclines. The median PFS was comparable to other standard single agents in the MBC setting.

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