Updated efficacy and safety of the j-alex study comparing alectinib (ALC) with crizotinib (CRZ) in ALK-inhibitor naïve ALK fusion positive non-small cell lung cancer (ALK+ NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9064-9064 ◽  
Author(s):  
Yuichi Takiguchi ◽  
Toyoaki Hida ◽  
Hiroshi Nokihara ◽  
Masashi Kondo ◽  
Young Hak Kim ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Kinase Inhibitor ◽  
Systemic Disease ◽  
Clinical Stage ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Superior Efficacy ◽  
Independent Review

9064 Background: ALC is a highly selective, CNS-active ALK tyrosine kinase inhibitor. In the J-ALEX study, ALC proved superior efficacy and tolerability compared to CRZ at the pre-planned interim analysis at 83 progression free survival (PFS) events (51% of target events) . Here we report the updated data with a further 10 months of follow up. Methods: Patients with advanced ALK+ NSCLC were randomized 1:1 to receive ALC 300 mg b.i.d or CRZ 250 mg b.i.d and stratified by ECOG PS, treatment line, and clinical stage. Study Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was PFS according to the blinded independent review. Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate and safety. Results: From Nov 2013 to Aug 2015, 207 patients were enrolled. Data cut off for the present analysis was Sep 2016. Median durations of PFS follow up were 20.5 months in the ALC arm and 20.4 months in the CRZ arm with 116 events by independent review observed. The updated PFS HR was 0.38 (95% CI: 0.26-0.55, p< 0.0001). Median PFS was 25.9 months (95% CI: 20.3-not estimated) with ALC and 10.2 months (95% CI: 8.3-12.0) with CRZ. For patients without brain metastasis at baseline (n = 164), ALC prevented CNS metastasis onset compared to CRZ (HR = 0.19, 95% CI: 0.07-0.53). For patients with brain metastasis at baseline (n = 43), ALC also prevented CNS progression compared to CRZ (HR = 0.51, 95% CI: 0.16-1.64). Adverse events (AEs) with frequency of more than 30% were constipation (37.9%) and nasopharyngitis (32.0%) in the ALC arm, while in the CRZ arm nausea (76.0%), diarrhea (74.0%), vomiting (57.7%), visual disturbance (54.8%), dysgeusia (51.9%), constipation (46.2%), increased ALT (32.7%), and increased AST (31.7%) were observed. Grade 3-4 AEs occurred with greater frequency in the CRZ arm (ALC: 32.0% vs CRZ: 56.7%). There were no Grade 5 AEs in either arm. Conclusions: In the updated analysis, ALC consistently showed superior efficacy compared to CRZ in systemic disease and prevention of CNS progression. ALC was also associated with a more favorable tolerability profile than CRZ. Clinical trial information: JapicCTI-132316.

Phase I study of irinotecan/5-fluorouracil/leucovorin (FOLFIRI) with sunitinib for advanced gastroesophageal cancers (EGC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15569-e15569
Author(s):  
Sarbajit Mukherjee ◽  
Christos Fountzilas ◽  
Patrick McKay Boland ◽  
Kristopher Attwood ◽  
Wei Tan ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Clinical Activity ◽  
Free Survival

e15569 Background: Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor with activity against VEGFR, PDGRF, KIT, FLT-3, and RET. S is synergistic with chemotherapy in preclinical models. We hypothesized that S+FOLFIRI combination will have increased efficacy in advanced EGC. Methods: This was a phase I study for patients with advanced chemo naïve EGC. Dose escalation used a standard 3+3 design. The primary objective was to determine the tolerability and safety of S+FOLFIRI. Secondary objectives were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Results: Twenty-three patients participated in the study (Male 78%, Female 22%). Median age was 60 (Range: 37-77) years. Median follow up time was 67.5 (95% CI: 58.9, 76) months. The most frequently reported adverse events were neutropenia (78%; G3/4: 43%), nausea (74%; G3/4:13%), diarrhea (65%; G3/4: 4%), vomiting (61%, G3/4: 9%) lymphopenia (52%; G3/4: 13%) and fatigue (52%; G3/4:17%).Two dose limiting toxicities (DLTs) were noted each at dose level (DL) 1 and 1A, one at DL 1B and 3 at DL 2 (Table 1). Maximum tolerated dose was determined at DL 1B. At the time of data reporting 21 patients had died. Two patients came off the study per investigator request. All patients were evaluated for efficacy. The median OS and PFS were 12.4 (95% CI: 8.9, 16.5) months and 6.2 (95% CI: 3.4, 13.5) months, respectively. Conclusions: S+FOLFIRI was reasonably tolerated, with a manageable safety profile and signs of clinical activity in patients with advanced EGC. This study was supported by a research grant from Pfizer, Inc. Clinical trial information: NCT00524186. [Table: see text]

Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9507-9507
Author(s):  
Reinhard Dummer ◽  
Keith Flaherty ◽  
Caroline Robert ◽  
Ana Maria Arance ◽  
Jan Willem de Groot ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Mek Inhibitor ◽  
Subsequent Treatment ◽  
Drug Discontinuation ◽  
Tolerability Profile

9507 Background: Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and OS and is standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here we report a 5-year update from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450 mg QD + binimetinib 45 mg BID (COMBO450), encorafenib 300 mg QD (ENCO300), or vemurafenib 960 mg BID (VEM). An updated analysis including PFS, OS, objective response rate (ORR; by blinded independent central review), and safety was conducted after minimum follow-up of 65.2 months (mo). Data are as is; study is ongoing. Results: At data cut-off (Sep 15, 2020), there were 131 (68%), 117 (60%), and 145 (76%) deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. The median OS (95% CI) and 5-year OS rate (95% CI) with COMBO450 were 33.6 (24.4–39.2) mo and 34.7% (28.0–41.5), respectively (median follow-up: 70.4 mo). The 5-year OS rate (95% CI) in COMBO450 pts who had normal lactate dehydrogenase (LDH) levels at baseline was 45.1% (36.5–53.2). Median OS and 5-year OS rates for ENCO300 and VEM, as well as for pts with normal and high LDH levels and > 3 organs involved at baseline, are shown in the table. For COMBO450, ENCO300, and VEM, the 5-year PFS rate was 22.9%, 19.3%, and 10.2%; ORR (95% CI) was 64.1% (56.8–70.8), 51.5% (44.3–58.8), and 40.8% (33.8–48.2); and the median duration of response (DOR) was 18.6, 15.5, and 12.3 mo, respectively. Safety results were consistent with the known tolerability profile of COMBO450. Additional efficacy and updated safety analyses will be presented. Following study drug discontinuation, the most common subsequent treatment in all arms was checkpoint inhibitors. Conclusions: Updated OS and DOR results with COMBO450 demonstrate continued long-term benefits in pts with BRAF V600-mutant melanoma. Clinical trial information: NCT01909453. [Table: see text]

scholarly journals Stereotactic Ablative Radiotherapy for the Management of Liver Metastases from Neuroendocrine Neoplasms: A Preliminary Study

2021 ◽  
Author(s):  
John Monte Hudson ◽  
Hans Tse-Kan Chung ◽  
William Chu ◽  
Amandeep Taggar ◽  
Laura Ellen Davis ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Local Control ◽  
Systemic Disease ◽  
Objective Response ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Response To Treatment ◽  
Neuroendocrine Neoplasms ◽  
Stereotactic Ablative Radiotherapy

Introduction: Liver metastases are common in patients with neuroendocrine neoplasms. The role of stereotactic ablative radiotherapy (SABR) is not well understood in this population. Objective: To evaluate the safety and efficacy of SABR in treating well-differentiated neuroendocrine liver metastases (WD-NELM). Methods: A retrospective review of patients with WD-NELM treated with SABR between January 2015-July 2019. Demographic, treatment and clinical/radiographic follow-up data were abstracted. RECIST 1.1 criteria were applied to each individual target to evaluate the response to treatment. Local control (LC) and progression free survival (PFS) were determined using Kaplan-Meier methodology. Toxicity was reported according to CTCAE v5.0. Results: Twenty-five patients with a total of 53 liver metastases treated with SABR were identified. Most patients (68%) had midgut tumors, were Grade II (80%) and had high volume intrahepatic and/or extrahepatic disease (76%). Median number of liver metastases treated was 2 with a median size of 2.5 cm. Median radiation dose delivered was 50Gy/5 fractions. Median follow-up was 14 months; 24 of the 25 patients were alive at time of analysis. The objective response rate (ORR) was 32%, with improvement or stability in 96% of lesions treated. The median time to best response was 9 months. The 1-year LC and PFS were 92% and 44% respectively. No Grade III/IV acute or late toxicity was identified. Conclusions: Liver SABR is a safe and promising means of providing local control for WD-NELM. This treatment modality should be evaluated in select patients in concert with strategies to manage systemic disease.

Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9071-9071
Author(s):  
Scott N. Gettinger ◽  
Rudolf M. Huber ◽  
Dong-Wan Kim ◽  
Lyudmila Bazhenova ◽  
Karin Holmskov Hansen ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Long Term Follow Up

9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [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]

A randomized, open-label, multicenter trial of the concurrent chemoradiotherapy of capecitabine with or without oxaliplatin versus cisplatin with 5-FU for Chinese squamous esophageal cancer: An interim report from CRTCOESC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4063-4063 ◽  
Author(s):  
Ruinuo Jia ◽  
Tanyou Shan ◽  
Fuyou Zhou ◽  
Anping Zheng ◽  
Lixin Wan ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Clinical Stage ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
High Rate ◽  
Interim Report ◽  
Open Label

4063 Background: CRT with 5- FU and cisplatin (PF) has shown greater clinical efficacy for local advanced esophageal cancer (EC) but with high rate of acute toxicities (ATs). CRTCOESC is a randomized, open-label, multicenter trial designed to evaluate the effect and safety of capecitabine with or without oxaliplatin versus PF with CRT in Chinese EC. Methods: Pts with biopsy-proven squamous EC (T2-4N0-2M0) were randomized to single capecitabine (Arm1), capecitabine plus oxaliplatin (Arm2), or PF (Arm3), while daily radiation 50Gy/2Gy for all. Pts were stratified by different regimens cycles. Both grade3-5 ATs and 2-year OS were the primary endpoint, with a planned accrual of 249 pts to detect a decrease in Grade3-5 ATs from 40% to 20%. The secondary endpoint included objective response rate (ORR) and 2-year progression free survival (PFS). Interim analysis of ATs and ORR was planned for the first 120 pts. Results: The study accrued 128 pts from 2014.10-2016.12, 118 were eligible. 86 patients were finished 16-weeks follow-up at least and analyzed in the interim report (Arm1: Arm2: Arm3 = 24: 37: 25). There was no difference between three arms on pts pretreatment characters (age, gender, weight, performance status, clinical stage, lymphonodus status, and pathology grade). Incidence of grade3-5 ATs in Arm1/2/3 were 25%: 32.4%: 64% ( p = 0.03); it was significantly lower in Arm1/2 than Arm3 (Arm1 vs Arm3, p = 0.041; Arm2 vs Arm3, p = 0.022); and there no meaningful different between Arm1 and Arm2 ( p = 0.738). The pCR rate and ORR were 50%: 48.6%: 48% and 87.5%: 83.8%: 100% in Arm1/2/3 ( p = 0.99; p = 0.133). 56 patients had been finished 1 year follow-up (Arm1: Arm2: Arm3 = 12: 26: 18). The 1-year OS and PFS were 75%: 91.9%: 76% and 66.7%: 62.2%: 60% in Arm1/2/3 ( p = 0.166; p= 0.926). Conclusions: Compared with PF, CRT with single capecitabine with or without oxaliplatin shown lower incidence of ATs and similar ORR and 1-year OS. The single capecitabine seemly carried out a benefit of lower ATs than it plus oxaliplatin; there was no meaningful difference for them on ORR and 1-year OS. Ruinuo Jia and Tanyou Shan did equal work. Clinical trial information: NCT02025036.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

A phase Ib study of TQB2450 plus anlotinib in patients with advanced triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1074-1074
Author(s):  
Jiayu Wang ◽  
Binghe Xu ◽  
Tao Sun ◽  
Quchang Ouyang ◽  
Yiqun Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Dose Escalation ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Expansion Phase ◽  
Qt Interval Prolongation ◽  
Grade 3

1074 Background: TQB2450 is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). Anlotinib is an antiangiogenic small molecule, multi-target tyrosine kinase inhibitor that has improved clinical outcomes in various solid tumors. This phase 1b study aims to evaluate the safety and efficacy of TQB2450 plus anlotinib for patients with advanced triple-negative breast cancer (TNBC) after the failure of standard therapy. Methods: This ongoing study included a dose-escalation phase and an expansion phase. Advanced TNBC patients with prior anthracyclines and/or taxanes treatment and failed at least first-line therapy were enrolled. In the dose-escalation phase, eligible patients received anlotinib (8mg, 10mg, and 12mg, qd, days 1-14; 21 days per cycle) plus TQB2450 (1200mg, day 1; 21 days per cycle) following the conventional 3+3 design. If the starting dose of 10mg anlotinib led to ≥2 dose-limiting toxicities (DLTs), 8mg anlotinib would be administered. After the dose-escalating phase, eligible patients were enrolled into the expansion cohort. The primary endpoint was objective response rate (ORR), and the secondary endpoints were overall survival (OS), disease control rate (DCR), progression-free survival (PFS), and safety. Results: Between May 29, 2019, and December 31, 2020, in the dose-escalation phase, three patients receiving 10mg anlotinib plus 1200mg TQB2450 had no DLTs in the first cycle, neither did three patients with 12mg anlotinib plus TQB2450. Next, 28 patients with advanced TNBC received 12 mg anlotinib plus TQB2450 in the expansion phase. Finally, a total of 34 patients were included with median age of 49.5 (32-70) and median prior lines of 2 (1-6). Numbers of patients with prior platinum therapy: 16, prior anthracycline therapy: 32. The ORR was 26.47% (9/34) and DCR was 82.35% (28/34). The median PFS was 8.57 months. Seventeen patients experienced grade 3 treatment-related AEs (TRAEs). Most frequently occurring (>5%) grade 3 TRAEs were QT interval prolongation (17.65%), hypertension (14.71%), diarrhea (8.82%), hand-foot syndrome (HFS) (8.82%), and hypertriglyceridemia (5.88%). Conclusions: TQB2450 plus anlotinib showed an acceptable safety profile with promising activity for previously anthracyclines and/or taxanes-treated advanced TNBC patients. Clinical trial information: NCT03855358 .[Table: see text]

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

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