Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

Subgroup analysis from JAVELIN Renal 101: Outcomes for avelumab plus axitinib (A + Ax) versus sunitinib (S) in advanced renal cell carcinoma (aRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Toni K. Choueiri ◽  
Robert J. Motzer ◽  
Matthew T. Campbell ◽  
Boris Y. Alekseev ◽  
Motohide Uemura ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Outcome Data ◽  
Once Daily ◽  
Free Survival ◽  
Independent Review ◽  
Secondary Endpoints ◽  
To Receive

544 Background: In the ongoing phase 3 JAVELIN Renal 101 trial, progression-free survival (PFS) was longer (median, 13.8 vs 8.4 mo; hazard ratio, 0.69; p=0.0001) and the objective response rate (ORR) was higher (51% vs 26%) with A + Ax vs S in patients with previously untreated aRCC. Here we report outcomes from an analysis of several prespecified subgroups. Methods: Patients were randomized 1:1 to receive A (10 mg/kg) IV every 2 weeks + Ax (5 mg) PO twice daily or S (50 mg) PO once daily for 4 wk (6-wk cycle). Primary and key secondary endpoints were PFS per independent review committee (IRC; RECIST v1.1) and OS in patients with PD-L1+ tumors (≥1% of immune cells) and in patients irrespective of PD-L1 expression; other secondary endpoints included OR per IRC (RECIST v1.1). Results: A total of 886 patients were randomized; 560 (63%) had PD-L1+ tumors. At data cut-off (Jun 2018), median follow-up was 12.0 vs 11.5 mo for A + Ax vs S groups. The table shows PFS and ORR by MSKCC and IMDC risk groups (F, favorable; I, intermediate; P, poor) and PD-L1 subgroup. Similar results for prognostic risk were seen in patients with PD-L1+ tumors. Outcome data (including PFS2) for additional clinical subgroups by baseline demographics and features will be presented. Clinical trial information: NCT02684006. Conclusions: A + Ax demonstrated PFS and OR benefit across all prognostic risk groups and PD-L1 subgroups vs S in aRCC.[Table: see text]

Efficacy and safety of avelumab plus axitinib (A + Ax) versus sunitinib (S) in elderly patients with advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 301-301
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Objective Response ◽  
Age Groups ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Age Group ◽  
Grade 3

301 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs S in patients with previously untreated aRCC. The role of immune checkpoint + VEGFR inhibition in elderly patients remains unclear. Here we report the efficacy of A + Ax vs S by age group from the second interim analysis (IA) of overall survival (OS) and the safety of A + Ax by age group from the first IA. Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1), OS, and safety by age group (<65, ≥65 to <75, and ≥75 y) were assessed. Results: A total of 271/138/33 and 275/128/41 patients in each age group (<65, ≥65 to <75, and ≥75 y, respectively) were randomized to the A + Ax or S arm, respectively. The proportion of IMDC risk groups was generally well balanced between the A + Ax and S arm in each age group, although in the ≥75 y age group, the frequency of patients with intermediate risk was slightly higher in the A + Ax arm, and that of patients with favorable risk was slightly higher in the S arm. The percentages of patients with favorable/intermediate/poor risk in each age group were 19%/61%/19%, 28%/58%/13%, and 12%/76%/12% in the A + Ax arm vs 20%/63%/16%, 23%/60%/16%, and 24%/61%/15% in the S arm. At data cut-off (Jan 2019) for the second IA, median follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by age group. In the A + Ax arm, the most common treatment-emergent adverse events (AEs) were diarrhea (62%/68%/42%), hypertension (49%/49%/55%), palmar-plantar erythrodysesthesia syndrome (37%/31%/15%), fatigue (37%/53%/30%), and nausea (34%/37%/21%) in each age group. Grade ≥3 treatment-emergent AEs and immune-related AEs were observed in 69%/74%/73% and 39%/40%/24% of patients in each age group, respectively. Conclusions: A + Ax demonstrated favorable efficacy across age groups, including patients aged ≥75 y. OS was still immature; follow-up for the final analysis is ongoing. The safety profile was generally consistent between age groups. Clinical trial information: NCT02684006 . [Table: see text]

Clinical outcomes of sunitinib (Su) for patients (pts) with desmoid tumors (DT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11052-11052
Author(s):  
Salvatora tindara Miano ◽  
Guido Francini ◽  
Serenella Civitelli ◽  
Roberto Petrioli ◽  
Edoardo Francini
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Radiological Progression ◽  
Once Daily ◽  
Free Survival ◽  
First Line Therapy ◽  
Secondary Endpoints ◽  
To Receive

11052 Background: The incidence of DT is steadily increasing in pts affected by familial adenomatous polyposis (FAP) and represents the first cause of death for pts who underwent preventive proctocolectomy. Currently, there is no standard therapy for DT and Tamoxifen (20 mg once daily) + Meloxicam (15 mg once daily) (TM) is the most commonly used regimen in clinical routine. We sought to evaluate the efficacy of Su, the most active PDGFR TKI, as first-line therapy for pts with DT. Methods: In this phase II IRB approved prospective study, pts with progressive, symptomatic, or recurrent DT were randomized to receive either Su (52 mg once daily) or TM. The primary end point was progression-free survival, defined as time from treatment start to clinical or radiological progression, whichever came first, at 2 years (2yr-PFS). Secondary endpoints were rates of objective response (OR), evaluated per RECIST criteria version 1.1, time to OR (ttOR), and toxicity. Adverse events (AE) were assessed per NCI-CTCAE version 4.02. Results: Of the 32 pts enrolled, 22 received Su and 10 TM. In both groups, median age at diagnosis was 43.5 years No OR was observed in the TM group. In the Su group, 17 pts had a partial response and 5 stable disease and the ORR was 75% (95% CI, 50 to 100). At a median follow-up of 27 months, the 2yr-PFS was 81% (95% CI, 69-96) and 36% (95% CI, 22-57) in the Su cohort and TM cohort, respectively (HR = 0.13; 95% CI, 0.05- 0.31; P<0.001). The median ttOR among pts who had an OR was 24 months. In the TM group, no toxicity was observed. The most frequently reported AE in the Su group were grade 1 or 2 hypothyroidism (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). (HR: 0.260; p = 0.0035). All AE responded to dose reduction (37.5 mg). Conclusions: In a cohort of pts with progressive, recurrent, or symptomatic DT, Su seems to be well tolerated and improve 2yr-PFS and OR rate compared with TM therapy. Further prospective studies with larger samples are needed to verify these results.

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

A randomized double-blind trial of carboplatin plus paclitaxel (CP) with daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo (PLA) in patients (pts) with previously untreated advanced non-small cell lung cancer (NSCLC):  NCIC Clinical Trials Group study BR29.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7511-7511 ◽  
Author(s):  
Scott Andrew Laurie ◽  
Benjamin J. Solomon ◽  
Lesley Seymour ◽  
Peter Michael Ellis ◽  
Glenwood D. Goss ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Vascular Endothelial ◽  
Double Blind ◽  
Free Survival ◽  
Endothelial Growth Factor ◽  
To Receive ◽  
Unacceptable Toxicity

7511 Background: In NCIC CTG study BR24, CED 30 mg/d + CP increased objective response rate (RR) and progression-free survival (PFS), but there were concerns regarding toxicity in some pts. BR29 tested a lower dose of CED 20 mg/d limiting accrual to pts without significant weight loss/hypoalbuminemia. Methods: Consenting, eligible adult pts with advanced incurable NSCLC of any histology were randomized to receive CED 20 mg/d or PLA with up to 6 cycles of C (AUC = 6) P (200 mg/m2); non-progressing pts continued CED/PLA after CP until progression, unacceptable toxicity or pt request. The primary endpoint was overall survival (OS). An interim analysis (IA) for PFS was planned after 170 events in the first 260 pts; the study would continue if the hazard ratio (HR) for PFS was < 0.7. Accrual continued until the required number of events was reached then held pending IA. Results: The trial was halted when the IA (n=260) revealed a HR for PFS of 0.89 (95% CI 0.66-1.20). A final analysis including all 306 randomized pts (median age 62, male 55%, PS 0 26%, PS 1 74%, adenocarcinoma 64%, squamous 13%, other histology 23%. RR was significantly higher with CED (52% vs 34 %, p = 0.001). For CED/PLA, respectively, median OS and PFS were 12.2/12.1 [HR: 0.95 (0.69-1.30, p=0.74)] and 5.5/5.5 months [HR: 0.91 (0.71-1.18, p=0.5)]. Grade >3 hypertension (15% vs 3%, p=0.0002), anorexia (7% vs 1%, p=0.02) and diarrhea (16% vs 1%, p<0.0001) were all significantly increased with CED; there were 2 deaths possibly-related to CED [1 each hemorrhage, leukoencephalopathy (prior radiation)]. Conclusions: Adding a lower dose of CED to CP increased RR and toxicity, but not PFS or OS.

Efficacy of pembrolizumab (pembro) monotherapy versus chemotherapy for PD-L1–positive (CPS ≥10) advanced G/GEJ cancer in the phase II KEYNOTE-059 (cohort 1) and phase III KEYNOTE-061 and KEYNOTE-062 studies.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Zev A. Wainberg ◽  
Charles S. Fuchs ◽  
Josep Tabernero ◽  
Kohei Shitara ◽  
Kei Muro ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Durable Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Positive Score ◽  
Combined Positive Score

427 Background: Pts with advanced gastric/gastroesophageal junction (G/GEJ) cancer received pembro monotherapy (200 mg Q3W) 3L+ in cohort 1 of KEYNOTE-059 (NCT02335411), 2L in KEYNOTE-061 (NCT02370498), or 1L in KEYNOTE-062 (NCT02494583). We present efficacy data for patients with PD-L1 combined positive score (CPS) ≥10 tumors in these trials. Methods: In study 059, 46 pts in cohort 1 with PD-L1 CPS ≥10 received pembro. In study 061, 108 pts with PD-L1 CPS ≥10 received pembro (n=53) or chemotherapy (chemo; n=55). In study 062, 182 pts with CPS ≥10 received pembro (n=92) or placebo + chemo (n=90). Efficacy end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Median follow-up in study 059 was 5.6 mo. Median OS with pembro was 7.9 mo (95% CI, 5.8-11.1), and 12-mo OS was 32.6%. PFS at 6 mo was 17.4%, ORR was 17.4%, and median DOR was 20.9 mo (2.8+ to 34.9+). In study 061, after a median follow-up of 8.8 mo, pembro prolonged OS vs chemo (median 10.4 vs 8.0 mo; HR, 0.64; 95% CI, 0.41-1.02); 12-mo OS was 45.3% for pembro and 23.6% for chemo. Median PFS was 2.7 mo for pembro and 3.4 mo for chemo (HR, 0.86; 95% CI, 0.56-1.33). ORR was 24.5% vs 9.1%, and median DOR was NR (4.1-26.0+) and 6.9 mo (2.6-6.9) for pembro vs chemo. In study 062, median follow-up was 17.4 mo for pembro and 10.8 mo for chemo. Pembro prolonged OS vs chemo (median 17.4 vs 10.8 mo; HR, 0.69; 95% CI, 0.49-0.97); 12-mo OS was 56.5% vs 46.7%. Median PFS was 2.9 mo vs 6.1 mo (HR, 1.09, 95% CI, 0.79-1.49). ORR was 25.0% vs 37.8%, and median DOR was 19.3 mo (1.4+ to 33.6+) vs 6.8 mo (1.5+ to 30.4+) for pembro vs chemo, respectively. Conclusions: Collectively, these data indicate that 1L, 2L, and 3L+ pembro monotherapy showed clinically meaningful efficacy in CPS ≥10, with a more durable response than chemotherapy. Clinical trial information: NCT02335411, NCT02370498, and NCT02494583. [Table: see text]

Efficacy of avelumab + axitinib (A + Ax) versus sunitinib (S) by IMDC risk group in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4574-4574
Author(s):  
John B. A. G. Haanen ◽  
James Larkin ◽  
Toni K. Choueiri ◽  
Laurence Albiges ◽  
Brian I. Rini ◽  
...  
Keyword(s):  
Risk Group ◽  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Complete Response ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Group A ◽  
To Receive

4574 Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), treatment-naive patients with aRCC receiving A + Ax showed improved progression-free survival (PFS) and objective response rate (ORR) across International Metastatic RCC Database Consortium (IMDC) risk groups (favorable [F], intermediate [I], and poor [P]) compared with patients receiving S. Here we report updated efficacy results for A + Ax vs S by IMDC risk groups from the third interim analysis. Methods: Patients were randomized 1:1 to receive either A (10 mg/kg intravenously every 2 weeks) plus Ax (5 mg orally twice daily) or S (50 mg orally once daily) for 4 weeks (6-week cycle). Patients were categorized per IMDC risk group into F, I, and P subgroups, and outcomes were assessed for F, I, P, and I + P. Overall survival (OS) and PFS, ORR, complete response (CR), and duration of response (DoR) per investigator assessment (RECIST v1.1) were assessed. Results: The study enrolled 886 patients with aRCC. At data cutoff (Apr 2020), median (95% CI) follow-up for OS in the A + Ax was NR (42.2-NE) vs 37.8 (31.4-NE) months with S. The Table shows OS, PFS, ORR, CR, and DOR by IMDC risk group. A + Ax generally showed improved efficacy compared with S across IMDC groups. Conclusions: Consistent with previously reported results from prior interim analyses, extended follow-up confirms the efficacy benefits of A + Ax vs S across IMDC risk groups in patients with aRCC. Patients continue to be followed up for the final OS analysis. Clinical trial information: NCT02684006. [Table: see text]

Consolidation with Alemtuzumab Improves Progression-Free Survival in Patients with Chronic Lymphocytic Leukemia (CLL) in First Remission - Long-Term Follow-Up of a Randomized Phase III Trial of the German CLL Study Group (GCLLSG).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 33-33 ◽  
Author(s):  
C. Schweighofer ◽  
M. Ritgen ◽  
B. Eichhorst ◽  
R. Busch ◽  
M. Kneba ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Consolidation Therapy ◽  
First Line ◽  
Phase Iii Trial ◽  
Free Survival ◽  
To Receive ◽  
Line Chemotherapy

Abstract Purpose: Alemtuzumab (MabCampath) is a humanized monoclonal antibody that targets the CD52 antigen, which is highly expressed on most human B and T lymphocytes. Alemtuzumab has shown considerable activity in both relapsed/refractory CLL and in the frontline treatment setting. In a recent study, treatment with single-agent alemtuzumab induced MRD-negative remissions in 20% of patients with relapsed/refractory CLL (Moreton et al JCO 2005;23:2971–2979). Other studies suggest that MRD negativity can also be attained when alemtuzumab is administered as consolidation for patients with CLL who achieve incomplete initial responses to chemotherapy. Here, we report our long-term experience within a randomized phase III trial that investigates the role of alemtuzumab for consolidation therapy in patients with previously untreated CLL. Methods: Pts in complete or partial remission after induction chemotherapy, with either fludarabine (F) or fludarabine plus cyclophosphamide (FC), were randomized to receive either alemtuzumab 30 mg, 3 times a week for ≤12 wks or no further treatment. Of 21 eligible pts, who had responded to induction with F or FC (1 CR, 1 nPR, 9 PRs), 11 pts (median age: 60 years) randomized to receive alemtuzumab consolidation and 10 to the observation arm. Pts in the alemtuzumab arm received standard premedication and infection prophylaxis with famciclovir and trimethoprim/sulfamethoxazole. Results: After a median follow-up of 48 months, calculated from time of randomization within this consolidation trial, progression-free survival (PFS) was significantly improved for pts who received alemtuzumab consolidation compared to those who received no further treatment (median PFS not reached versus 20.6 months, P = 0.004). PFS from the beginning of induction therapy with F or FC is also significantly greater for patients in the alemtuzumab consolidation arm versus the observation arm. So far, 3 of 11 pts presented with disease progression after alemtuzumab consolidation compared with 8/10 progressing pts in the observation arm. Differences in PFS between both arms were not associated with disease stage before first line treatment, type of first line chemotherapy (F vs. FC) or response status before initiation of consolidation therapy (CR vs. nPR vs. PR). Correlations between achievement of MRD negative responses and PFS is still under investigation and is planned for presentation. With the exception of 2 patients (1 pt in each arm) all patients remain alive. The study was stopped prematurely due to severe infections (7 CTC III infections, which included 4 CMV reactivations, 1 CTC IV infection) in 7/11 patients being treated with alemtuzumab. However, these infections were successfully treated, not associated with the cumulative dose of alemtuzumab, and no late complications of consolidation therapy have been observed. Conclusions: Although based on few pts due to incomplete accrual, long-term PFS was significantly prolonged in patients with CLL receiving alemtuzumab consolidation after first line chemotherapy with F or FC. An ongoing phase I/II trial of the GCLLSG (CLL2i) is currently evaluating the optimal dose and schedule of alemtuzumab in CLL pts after fludarabine-based chemotherapy.

Second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (mCRC) patients (pts) who progressed to a first-line treatment containing BV: Updated results of the phase III “BEBYP” trial by the Gruppo Oncologico Nord Ovest (GONO).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3615-3615 ◽  
Author(s):  
Gianluca Masi ◽  
Fotios Loupakis ◽  
Lisa Salvatore ◽  
Chiara Cremolini ◽  
Lorenzo Fornaro ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Phase Iii Study ◽  
Reported Data ◽  
To Receive ◽  
Clinical Trial Information

3615 Background: Retrospective data suggested that the continuation of BV with second-line CT beyond progression (PD) in pts who received BV in first-line can improve the outcome. Recently, results of the AIO/AMG ML18147 study demonstrated an improved overall survival (OS) by continuing BV beyond PD. Methods: This phase III study randomized pts with measurable mCRC treated in first-line with BV plus fluoropyrimidine, FOLFIRI, FOLFOX or FOLFOXIRI, to receive in second-line mFOLFOX6 or FOLFIRI (depending on first-line CT) with or without BV. The primary end-point was progression free survival (PFS).To detect a HR for PFS of 0.70 with an α and β error of 0.05 and 0.20 respectively, the study required 249 events. Assuming an accrual time of 24 months (mos) and a follow up of 12 mos we planned to randomize 262 pts. Results: Considering the results of the AIO/AMG ML18147 trial, the study accrual was stopped prematurely. A total of 185 pts were randomized and 184 pts were included in the ITT analysis (1 pt randomized in error). Pts characteristics were (arm A/arm B): number 92/92, gender M75%-F25%/M57%-F43%, median age 66 (38-75)/62 (38-75) years, PS=0 82%/82%, multiple site of disease 76%/77%. At a median follow up of 18 mos the study met its primary endpoint by improving PFS in the BV arm. We updated results and at a median follow up of 22 mos the improvement in PFS for the experimental arm was confirmed with a median PFS of 5.2 mos for arm A and 6.7 mos for arm B (HR=0.66; 95% CI 0.49–0.90; unstratified p=0.0072). Subgroup analyses showed a consistent benefit in all subgroups including gender (F: HR=0.63; M: HR=0.72) and first-line PFS (≤10 mos: HR=0.57; >10 mos: HR=0.71). Response rates (RECIST) were 18% and 21% (p=0.71). Toxicity profile was consistent with previously reported data. The OS data are still immature, with 56 events in arm A and 54 in arm B and the median OS is 16.0 mos and 16.5 mos respectively (HR=0.83; 95% CI 0.57-1.22; unstratified p=0.34). Conclusions: This study demonstrates an improvement in PFS by continuing BV in second-line in pts who had received CT+BV in first-line. Clinical trial information: NCT00720512.

Time to central nervous system (CNS) metastases (mets) with atezolizumab (A) or placebo (P) combined with cobimetinib (C) + vemurafenib (V) in the phase III IMspire150 study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10023-10023 ◽  
Author(s):  
Paolo Antonio Ascierto ◽  
Caroline Robert ◽  
Karl D. Lewis ◽  
Rodrigo Munhoz ◽  
Gabriella Liszkay ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Free Survival ◽  
History Of ◽  
To Receive

10023 Background: The phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival with first-line combination treatment with A+C+V vs P+C+V in patients (pts) with previously untreated BRAFV600 mutation–positive advanced melanoma. Here we report incidence and time to development of CNS mets with A+C+V vs P+C+V in the IMspire150 study. Methods: Eligible pts were randomized 1:1 to receive A+C+V or P+C+V. A or P were given on day 1 and 15 of each 28-day cycle after an initial cycle of C+V. Incidence and time to development of CNS mets were evaluated in pts with no history of CNS mets at baseline confirmed by magnetic resonance imaging/computed tomography (MRI/CT). On study MRI/CT assessments were performed as clinically indicated. Time-to-event outcomes were estimated using the Kaplan-Meier method and competing risks analysis. Sensitivity analyses were conducted using landmark analysis at time of initiation of A or P. Results: 514 pts were randomized to receive A+C+V (n = 256) or P+C+V (n = 258); 244 and 247 pts, respectively, had no history of CNS mets at baseline. After a median follow-up of 18.9 months, CNS mets had developed in 52/244 pts (21%) in the A+C+V arm and 62/247 pts (25%) in the P+C+V arm. In both arms, pts with CNS mets were more likely to have other known unfavorable prognostic factors: elevated LDH, presence of liver mets, and/or higher tumor burden. Cumulative incidence of CNS mets as first site of progressive disease with A+C+V vs P+C+V was 8% vs 9%, 16% vs 19%, 20% vs 24%, and 23% vs 26% at 6, 12, 18, and 24 months, respectively (hazard ratio [HR] 0.87; 95% CI 0.60-1.26). Estimated CNS mets-free survival rates for A+C+V vs P+C+V were 91% vs 90%, 81% vs 75%, 74% vs 66%, and 69% vs 62% at 6, 12, 18, and 24 months, respectively, with a trend for improved CNS mets-free survival with A+C+V (HR 0.79; 95% CI 0.55-1.14). Results of landmark analyses for CNS mets-free survival and cumulative incidence of CNS mets were similar to those in the overall analysis. Conclusions: The addition of anti–programmed death-ligand 1 to C+V is associated with numerically lower rates of interval development of CNS mets, consistent with the overall benefit observed for A+C+V in the study. This finding requires further follow-up to fully assess the magnitude of benefit of A+C+V on CNS mets-free survival. Clinical trial information: NCT02908672.

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