scholarly journals Impact of Baseline Covariates and Prior Therapy on the Efficacy of Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

2014 ◽  
Vol 25 ◽  
pp. iv187 ◽  
Author(s):  
M. Peeters ◽  
T. Price ◽  
A. Cervantes ◽  
A. Sobrero ◽  
M.P. Ducreux ◽  
...  
Keyword(s):  
Second Line ◽  
Prior Therapy ◽  
Baseline Covariates

Second-line bosutinib (BOS) for patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML): Final 10-year results of a phase 1/2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7009-7009
Author(s):  
Carlo Gambacorti-Passerini ◽  
Tim H. Brümmendorf ◽  
Dong-Wook Kim ◽  
Yeow Tee Goh ◽  
Irina S Dyagil ◽  
...  
Keyword(s):  
Phase 1 ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Second Line ◽  
Prior Therapy ◽  
Kaplan Meier ◽  
Imatinib Resistant

7009 Background: BOS is approved for Philadelphia chromosome (Ph)+ CML resistant/intolerant to prior therapy and newly diagnosed Ph+ CP CML. In a phase 1/2 study, second-line BOS showed durable efficacy and manageable toxicity in pts with imatinib-resistant (IM-R) or -intolerant (IM-I) Ph+ CP CML. Methods: This final efficacy and safety analysis of the phase 1/2 study and extension study was based on ≥10 y of follow-up (FU). Ph+ CP CML pts who received BOS starting at 500 mg/d after prior treatment (Tx) with imatinib only were included. Results: 19% of pts were on BOS at y 10, and 13% were still on BOS at study completion after ≥10 y; 19% completed ≥10 y of FU. Median duration of Tx and FU were 26 and 54 mo, respectively. Median (range) dose intensity was 436 (87–599) mg/d. The most common primary reasons for permanent Tx discontinuation were lack of efficacy (unsatisfactory response or disease progression; 27%) and adverse events (AEs; 26%). In pts with a valid baseline assessment, cumulative complete cytogenetic response (CCyR), major molecular response (MMR) and MR4 rates (95% CI), respectively, were 50% (43–56), 42% (35–49) and 37% (30–44) (IM-R: 48% [41–56], 46% [37–55] and 39% [31–48]; IM-I: 53% [41–64], 36% [25–48] and 33% [22–45]). Responses were durable, with estimated probabilities of maintaining CCyR, MMR and MR4 > 50% after ≥10 y (Table). At 10 y, cumulative incidence of on-Tx progression/death was 24% and Kaplan-Meier (K-M) overall survival 72% (Table); 55 deaths (IM-R: n = 41; IM-I: n = 14) occurred on study, none BOS-related. Any grade Tx-emergent AEs (TEAEs) in ≥40% of pts were diarrhea (86%), nausea (46%) and thrombocytopenia (42%). Pleural effusion, cardiac and vascular TEAEs occurred in 13%, 12% and 11% of pts, respectively. 28% of pts had AEs leading to permanent Tx discontinuation; most common (≥2% of pts) were thrombocytopenia (6%), neutropenia (2%) and alanine aminotransferase increased (2%). Conclusions: These 10-y data are consistent with prior results of durable efficacy and manageable toxicity with second-line BOS and support long-term BOS use in CP CML pts after imatinib failure. Clinical trial information: NCT00261846 and NCT01903733. [Table: see text]

Two-Year Consolidation By Nilotinib Is Associated with Successful Treatment Free Remission in Chronic Myeloid Leukemia with MR4.5: Subgroup Analysis from STAT2 Trial in Japan

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1889-1889 ◽  
Author(s):  
Naoto Takahashi ◽  
Chiaki Nakaseko ◽  
Kaichi Nishiwaki ◽  
Hisashi Wakita
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Subgroup Analysis ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Second Generation ◽  
Second Line ◽  
First Line ◽  
Prior Therapy ◽  
Line Therapy ◽  
Treatment Free Remission

Abstract Background Nilotinib (NIL) is a second-generation tyrosine kinase inhibitor (TKI) that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). Superior rates of deeper molecular responses (DMR) were achieved with NIL vs. imatinib (IM) in patients newly diagnosed with CML in chronic phase (CML-CP) in the ENESTnd trial. In addition, the ENESTcmr study demonstrated that switching to NIL after a minimum of 2 years on IM led to increased rates of DMR vs. remaining on IM. Switching to NIL treatment for 2 years safely led to MR4,5 (BCR-ABLIS…0.0032%) in 47.5% of patients with major molecular response (MMR) on long-term IM therapy in our STAT1 trial. Recently, treatment free remission (TFR) was proposed as one of the goals in CML treatment. Indeed, prospective trials suggest that IM therapy may be safely and successfully discontinued in 40% of CML patients with MR4.5. STAT2 is the first study to evaluate the efficacy of two-year consolidation by NIL for successful TFR in patients with CML-CP who had achieved MR4.5. Before enrolling in STAT2, some patients were treated by not only IM but also NIL because of MMR but no MR4.5 after IM therapy, and some patients changed over from STAT1 to STAT2. Here, we present the results of the subgroup analysis from STAT2 based on the prior treatments at the time of entry into the study. Methods In the STAT2 trial, patients who achieved MR4.5 on IM front line therapy (subgroup 1; SG1) or NIL second line therapy after IM therapy (subgroup 2; SG2) were eligible and NIL was given twice daily at the dose of 600 mg/day for 2 years in consolidation phase. The primary endpoint of STAT2 was the proportion of patients with successful TFR, defined as no confirmed loss of MR4.5 (2 consecutive IS RQ-PCR tests), within the first 12 months of TFR phase. Thirty-five institutions in STAT study group participated. The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was signed by all patients according to institutional guidelines. The study was approved by all institutional review boards and registered with UMIN-CTR (000005904). Results Between July 2011 and December 2012, 96 patients were enrolled in STAT2. Among 96 patients, 50 patients were treated by IM first line only as prior therapy (SG1). On the other hand, 40 patients were treated by IM first line and NIL second line including 21 patients who changed over from STAT1 to STAT2 because they achieved MR4.5 (SG2). Six patients were excluded in this analysis because second generation TKIs were taken as a first line therapy. Among patients treated by NIL for 2 years in this study, 40/50 (80%; 95% CI, 68.4%-88.7%) in SG1 and 33/40 (82.5%; 95% CI, 69.6%-91.5%) in SG2 entered the TFR phase, respectively. The median age was 54.5 years in SG1 and 56.0 years in SG2. The ratio of men to women was 26:14 in SG1 and 18:15 in SG2. The total duration of TKI treatment was 110 months for the SG1 with a median of 86 months of IM, and 24 months of NIL, and 93 months in SG2 with a median of 62 months of IM, and 31 months of NIL,, respectively. All patients achieved MR4.5 at the time of entry into the study and the median time to MR4.5 was 47 months in SG1 and 60 months in SG2.The proportion of patients who maintained TFR at 12 months after stopping NIL was similar across the 2 subgroups: 25/40 (62.5%; 95% CI, 48.3%-77.3%) in SG1, and 23/33 (69.7%; 95% CI, 54.0%-82.5%) in SG2. The Kaplan-Meier (KM) analysis of TFR survival showed that in the 2 subgroups, the majority of events occurred within the first 6 months after stopping NIL (Figure 1). There were no significant differences between these 2 subgroups. Conclusion After two-year consolidation by NIL of CML-CP patients who achieved MR4.5, the TFR rate was 67.9% (90%CI: 58.2% to 76.6%) at 12 months in the STAT2 trial. In the present analysis looking at the prior TKI exposure, the TFR rate was similar in patients treated with IM first line only or who switched from IM to NIL before entering the study, despite the fact that the treatment duration of switched patients was slightly shorter. These findings suggest that two-year consolidation by NIL is associated with successful TFR in CML with MR4.5 that was achieved with IM alone or after switching to NIL. Figure Kaplan-Meiercurve of TFR survival in the 2 subgroups based onthe prior treatmentsbefore two-year consolidation by NIL, IM first line only as prior therapy (subgroup1) and IM first line and NIL second line (subgroup2). Figure. Kaplan-Meiercurve of TFR survival in the 2 subgroups based onthe prior treatmentsbefore two-year consolidation by NIL, IM first line only as prior therapy (subgroup1) and IM first line and NIL second line (subgroup2). Disclosures Takahashi: PFIZER: Honoraria, Research Funding; BMS: Honoraria; NOVARTIS PHARMA: Honoraria, Research Funding. Nakaseko:BMS: Honoraria, Research Funding; PFIZER: Honoraria, Research Funding; NOVARTIS: Honoraria. Nishiwaki:Novartis PHARMA: Research Funding.

Impact of response to prior chemotherapy (RTPC) on outcomes in second-line therapy for advanced urothelial carcinoma (UC): Implications for trial design.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4539-4539
Author(s):  
Gregory Russell Pond ◽  
Joaquim Bellmunt ◽  
Ronan Fougeray ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Multivariable Analysis ◽  
Prognostic Impact ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Prior Chemotherapy ◽  
Prior Therapy ◽  
Line Therapy ◽  
The Impact

4539 Background: Performance status (PS), hemoglobin (Hb), liver metastasis (LM), and time from prior chemotherapy (TFPC) are significant prognostic factors in second-line therapy for advanced UC. Setting of prior chemotherapy, i.e., metastatic or perioperative, has not appeared significant. However, the impact of prior chemosensitivity is unclear, which may confound trial interpretation. Hence, we examined the prognostic impact of RTPC, when prior therapy was given for metastatic disease. Methods: Six phase II trials evaluating second-line chemotherapy and/or biologics (n=504) were pooled. Patients who received prior therapy for metastatic disease were eligible for analysis if data regarding Hb, LM, PS, and TFPC were available. Response by RECIST to first-line therapy was recorded. Progression-Free Survival (PFS) and overall survival (OS) were calculated from the date of registration using the Kaplan-Meier method. Results: 275 pts were evaluable for analysis. Patients received gemcitabine-paclitaxel, cyclophosphamide-paclitaxel, pazopanib, docetaxel plus vandetanib/placebo or vinflunine (2 trials). Those with prior response (n=111) had a median (95% CI) OS of 8.0 (6.8-9.4) months (mo) and PFS of 3.0 (2.6-4.0), compared with OS and PFS of 5.9 (5.0-6.6) mo and 2.6 (2.0-2.8) for those without prior response (n=164). Multivariable analysis did not reveal an independent impact of RTPC on PFS or OS (Table). Conclusions: RTPC in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced UC. Patients who received prior chemotherapy in peri-operative or metastatic settings may be enrolled in the same second-line trial stratified for PS, anemia, LM and TFPC. [Table: see text]

Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Kristen Bibeau ◽  
Luis Féliz ◽  
Scott Barrett ◽  
Ling Na ◽  
Christine Francis Lihou ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.

Early-phase trials compared to first- and second-line FDA-approved treatments in patients with advanced gallbladder cancer and cholangiocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13020-e13020
Author(s):  
Ishwaria Mohan Subbiah ◽  
Apostolia Maria Tsimberidou ◽  
Aung Naing ◽  
Vivek Subbiah ◽  
Ahmed Omar Kaseb ◽  
...  
Keyword(s):  
Phase I ◽  
Drug Administration ◽  
Univariate Analysis ◽  
Hepatic Arterial Infusion ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Phase I Trials ◽  
Second Line ◽  
Prior Therapy ◽  
Metastatic Setting

e13020 Background: Patients with advanced cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few effective therapeutic options. We compared prognostic factors and clinical outcomes of CC/GC pts treated on phase I trials with that of their first-, second-line and last Food and Drug Administration (FDA)-approved therapy given in setting of metastatic disease. Methods: We retrospectively reviewed electronic medical records of patients with GC and CC evaluated in the phase I program clinic from November 2004 to March 2011. Results: Of the 72 patients with CC or GC, 32 (44%) were not enrolled on a trial mainly due to clinical deterioration (n=25). Of 40 treated patients (GC=6; CC=34; median age 60 years; median prior systemic therapies = 3), 8 (20%) had stable disease (SD) > 6 months; 3 (8%) achieved a partial response (PR); SD > 6 months/PR was observed mainly on protocols with hepatic arterial infusion drug administration and/or angiogenic inhibitors, anti-her2/neu agents or a novel MAPK/ERK kinase (MEK) inhibitor. Median progression-free survival (PFS) on phase I trials was 2.0 months (95% CI 1.7, 2.8) versus 3.0 months (95% CI 2.4, 5.0; p=0.95), 3.0 months (95% CI 2.3, 4.6; p=0.98), and 3.0 months (95% CI 2.4, 3.9; p=0.79) for their first-, second-, and last systemic therapy with FDA-approved agents given in the metastatic setting, respectively. In univariate analysis, factors associated with a shorter Phase I PFS were > 3 metastatic sites, elevated ALT (>56 IU/L), serum creatinine (>1.6mg/dL), and CA19-9 (>35U/mL). Conclusions: In heavily pretreated patients, PFS in the clinical trials setting remained poor but did not differ significantly from that of their first-line, second-line, and last prior therapy with FDA-approved agents. Response rate (SD >6 months/PR) of 28% was seen in trials with locoregional treatment or inhibitors of angiogenesis, her2/neu or MEK.

Phase III AXIS trial for second-line metastatic renal cell carcinoma (mRCC): Effect of prior first-line treatment duration and axitinib dose titration on axitinib efficacy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 354-354 ◽  
Author(s):  
Brian I. Rini ◽  
Bernard J. Escudier ◽  
M Dror Michaelson ◽  
Sylvie Negrier ◽  
Martin Eric Gore ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Dose Titration ◽  
Second Line ◽  
First Line ◽  
Sunitinib Treatment ◽  
Prior Therapy

354 Background: Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. In the phase 3 AXIS trial of axitinib vs sorafenib for second-line mRCC, axitinib significantly prolonged median progression-free survival (mPFS) (6.7 vs 4.7 months; hazard ratio 0.665; P<0.0001). Here, we evaluated the effect of prior sunitinib treatment duration and axitinib dose titration on subsequent axitinib efficacy. Methods: Eligible patients had clear-cell mRCC; measurable RECIST-defined progressive disease after 1 prior first-line systemic therapy; and Eastern Cooperative Oncology performance status (PS) 0/1. Patients were stratified by PS and prior therapy, and randomized 1:1 to either axitinib, at a starting dose of 5 mg twice daily (BID), or sorafenib, 400 mg BID. Patients without toxicity >grade 2 and BP <150/90 mmHg without antihypertensive medication for >2 weeks were eligible to increase axitinib dose to 7 mg BID and then to 10 mg BID. Results: The mPFS for patients receiving at least one total daily axitinib dose >10 mg (dose-titrated group; n=132) was 6.6 months [95% CI 4.7–8.3] and 8.3 months [95% CI 6.0–10.2] for patients receiving axitinib ≤10 mg (n=227). A total of 194 patients (53.7%) in the axitinib arm and 195 patients (53.9%) in the sorafenib arm had prior sunitinib treatment. The mPFS for patients with duration of prior sunitinib treatment ≥6 months and <6 months were 4.8 months [95% CI 4.5–6.5] and 4.6 months [95% CI 2.8–8.3] for axitinib patients; and 4.6 months [95% CI 2.9–4.9] and 2.9 months [95% CI 2.8–4.6), for sorafenib patients. The mPFS for duration of prior sunitinib ≥9 months and <9 months were 6.3 months [95% CI 4.6–6.7] and 4.5 months [95% CI 2.8–6.4] for axitinib patients; and 4.6 months [95% CI 2.8–4.9] and 2.9 months [95% CI 2.8–4.7]) for sorafenib patients. Conclusions: Duration of prior sunitinib ≥9 months may be associated with a longer PFS on second-line VEGFR tyrosine kinase inhibitors. Both axitinib dose-increased and non-increased patients had longer PFS compared with the sorafenib arm.

Lenalidomide in Combination with Dexamethasone Is More Effective Than Dexamethasone at First Relapse in Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3552-3552 ◽  
Author(s):  
Edward Stadtmauer ◽  
Donna Weber ◽  
M. Dimopolous ◽  
Andrew Belch ◽  
Michel Attal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Response Rate ◽  
Response Rates ◽  
High Dose ◽  
Cell Transplant ◽  
Second Line ◽  
Prior Therapy ◽  
First Relapse ◽  
Line Of Therapy

Abstract Background: High-dose dexamethasone (Dex) remains a standard therapy for relapsed or refractory multiple myeloma (MM). Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with Dex. At the interim analysis, lenalidomide/dexamethasone achieved a significant benefit over dexamethasone, providing a longer median time to progression (TTP), higher response rates, and higher CR rates. Aim: This prospective subgroup analysis of MM-009/010 was performed to determine the potential benefit of starting lenalidomide/dexamethasone at first relapse by analyzing outcomes with lenalidomide/dexamethasone versus dexamethasone among patients who had received only 1 versus > 1 prior line of therapy. Methods: Patients who had received at least 1 prior treatment and were not refractory to dexamethasone were randomized to either receive oral lenalidomide (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on Days 1–4, 9–12, 17–20 every 4 weeks for 4 months, then 40 mg on Days 1–4 every cycle thereafter) or placebo plus Dex. The European Blood and Marrow Transplantation criteria were used to evaluate response. Randomization was stratified at entry by number of prior therapies (1 versus > 1). Results: Among the 248 patients who had received only 1 prior therapy, those receiving second-line lenalidomide/dexamethasone had a significantly longer median TTP (71 vs. 20 wks) and a higher response rate (complete response [CR] + partial response [PR]; 65% vs. 26%) versus those receiving second-line dexamethasone. Among the 456 patients who had received > 1 prior line of therapy, the median TTP (41 vs. 20 wks), response rate (58% vs. 20%) were higher with lenalidomide/dexamethasone compared with dexamethasone. Comparing patients who received lenalidomide/dexamethasone as second-line versus as later salvage therapy, the median TTP appeared longer and the response rates higher in patients who received lenalidomide/dexamethasone earlier, although TTP and response rates were also significantly better with lenalidomide/dexamethasone than with dexamethasone in patients who received lenalidomide/dexamethasone later. Differences in the groups included prior stem cell transplant (66% vs. 54%), thalidomide (12.5% vs. 53.2%), and bortezomib (0.4% vs. 11.6%) in the second-line versus later salvage therapy groups. No difference was observed in grade ¾ adverse events or survival with a median follow-up of 16.8 months. Conclusions: Lenalidomide/dexamethasone provided higher response rates and improved TTP compared with dexamethasone at first relapse and beyond. Response to lenalidomide/dexamethasone was superior to that to dexamethasone regardless of the type of prior therapy. TTP and response rates appeared more favorable when lenalidomide/dexamethasone was administered earlier at first relapse compared with its use as later salvage therapy. These data support the use of lenalidomide/dexamethasone for patients as second-line therapy.

scholarly journals Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition

2021 ◽  
Author(s):  
Thomas E Lew ◽  
Victor S Lin ◽  
Edward Robert Scheffer Cliff ◽  
Piers Blombery ◽  
Ella R Thompson ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Unmet Need ◽  
Lymphocytic Leukemia ◽  
Second Line ◽  
Prior Therapy ◽  
Resistant Disease ◽  
Dismal Prognosis ◽  
Improved Outcomes ◽  
Bruton Tyrosine Kinase ◽  
Targeted Agent

Covalent Bruton tyrosine kinase inhibitors (BTKis) and the BCL2 inhibitor venetoclax have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), especially those with biologically adverse disease. Patients with CLL resistant to their first targeted agent (TA) can be effectively treated with the alternative class. However, relapses are expected with second-line TA therapy, and the clinical challenge of double class-resistant disease is now emerging with increasing frequency. To define the characteristics and outcomes of patients with double class-resistant disease, we retrospectively analyzed 17 patients who developed progressive disease (PD) on both TA classes for CLL (venetoclax, then BTKi, n=12; BTKi, then venetoclax, n=5). The cohort was heavily pre-treated (median lines of prior therapy: 4) and enriched for adverse disease genetics (complex karyotype: 12/12 tested, 100%; del(17p)/TP53 mutations: 15/17, 88%). The median time to progression on prior venetoclax was 24 (range 6-94) months, and on prior BTKi was 25 (range 1-55) months. Progression on second-line TA was manifest as progressive CLL in 11 patients and as Richter transformation in six. The median overall survival after progression on second-line TA was 3.6 (95%CI 2-11) months. Patients with double class-resistant CLL have a dismal prognosis, representing a group of high unmet need.

Everolimus (EVE) plus endocrine therapy in patients with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (BC): First- and second-line data from the BOLERO-4 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1010-1010 ◽  
Author(s):  
Fatima Cardoso ◽  
Cristian Villanueva ◽  
Melanie Royce ◽  
Felipe Cruz ◽  
Marc Debled ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adverse Events ◽  
Disease Progression ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Second Line ◽  
Prior Therapy ◽  
Estrogen Receptor Positive

1010 Background: Initial first-line (1L) data from the phase 2 BOLERO-4 (NCT01698918) study of EVE + letrozole (LET) in postmenopausal patients (pts) with ER+, HER2− metastatic BC (MBC) or locally advanced BC (LABC) have been previously reported. Here, we present updated 1L progression-free survival (PFS) data, plus new data describing second-line (2L) EVE + exemestane (EXE) in pts with disease progression after EVE + LET. Methods: Postmenopausal pts with ER+, HER2− MBC or LABC with no prior therapy for advanced disease received EVE 10 mg/day + LET 2.5 mg/day. After disease progression, pts could receive EVE + EXE 25 mg/day until further disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint: 1L PFS. Secondary endpoints: overall response rate (ORR), clinical benefit rate (CBR), 2L PFS, overall survival (OS), and safety (1L and 2L). Results: Among 202 pts (median age, 64 years) with 1L MBC (96%) or LABC (4%), median PFS (95% CI) was 21.7 (18.1–23.9) months, ORR was 43.6%, and CBR was 74.3%. 42 pts (median age, 62 years) with MBC (88%) or LABC (12%) who progressed on 1L EVE + LET received optional 2L EVE + EXE. 2L median PFS (95% CI) was 3.7 (1.8–9.1) months, ORR was 4.8%, and CBR was 21.4%. Common 1L adverse events (all grades, regardless of drug relationship) were stomatitis (69%), weight loss (44%), diarrhea (40%), nausea (37%), and anemia (35%); 2L adverse events included stomatitis (19%) and weight loss (19%). Median duration of follow-up from start of 1L to the data cutoff for these new analyses (17 June 2016) was 23.5 months. OS will be analyzed at a later data cut. Conclusions: EVE + LET is an effective regimen in 1L ER+, HER2− advanced BC. Thesedata support previously reported BOLERO-2 data demonstrating a PFS improvement from addition of EVE to an aromatase inhibitor. 2L data, although limited by the small number of pts, show preliminary evidence of EVE activity when continued beyond disease progression. No new safety signals were seen. Lower rates of stomatitis in 2L were noted. Clinical trial information: NCT01698918.

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