Exploratory endpoints in a FARETES study of the efficacy of testosterone in metastatic renal cell carcinoma (mRCC) patients.

574 Background: In multicenter randomized phase 2 study (FARETES) we showed that male patients with mRCC receiving targeted therapy had significantly less fatigue and better symptom control with testosterone undecanoate (T) (MASCC 2018, LBA004). Here we described exploratory endpoints in FARETES study. Methods: Sixty male patients with clear cell mRCC, normal PSA level, low testosterone level and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either T (Nebido, 1,000 mg) and targeted therapy or targeted therapy alone (control group). T was injected intramuscular deeply on Day 1 of a new treatment cycle. Exploratory endpoints included rate of adverse events (AE) of targeted therapy, duration of targeted therapy, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: As of the data cutoff on October 17, 2018, median (range) follow-up was 15.2 (9.9 -16.5) months. No unexpected toxicity of T was observed. Grade 3-4 targeted therapy-related AE occurred in 11 (37%) and 3 (10%) patients in the control group and T group, respectively. Discontinuation due to AE was observed in 3% (1/30) of patients in the T group and in 17% (5/30) of patients in the control group. ORR and PFS were significantly better in the T group (all P < 0.05, Table). Median OS was not reached in either group. Clinical trial information: NCT03379012. Conclusions: T therapy could decrease rate of serious AE of targeted therapy. Male mRCC patients receiving T had longer duration of targeted therapy, better PFS and ORR. Larger trials are needed to evaluate efficacy of T in this group of patients.[Table: see text]

Download Full-text

151 A RANDOMIZED,OPEN CLINICAL TRIAL TO COMPARE THE EFFICACY AND SAFETY OF ANLOTINIB PLUS IRINOTECAN VERSUS IRINOTECAN IN PATIENTS WITH ESCC

Diseases of the Esophagus ◽

10.1093/dote/doab052.151 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Feng Wang ◽

Xiangrui Meng ◽

Hangrui Liu ◽

Qingxia Fan

Keyword(s):

Disease Control ◽

Phase Ii ◽

Phase Ii Trial ◽

Objective Response ◽

Progression Free Survival ◽

Thyroid Stimulating Hormone ◽

Disease Control Rate ◽

Control Group ◽

Trial Group ◽

Grade 3

Abstract The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC. Methods We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS). Results Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (>10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups. Conclusion Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.

Download Full-text

Does the addition of molecular targeted therapy to standard treatments lead to better or worse outcomes overall? A systematic review of EGFR-targeted therapies used in combination with standard treatments.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2572 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2572-2572 ◽

Cited By ~ 1

Author(s):

Jennifer Rauw ◽

Marguerite Ennis ◽

Monika K. Krzyzanowska ◽

Srikala S. Sridhar

Keyword(s):

Systematic Review ◽

Radiation Therapy ◽

Targeted Therapy ◽

Hormonal Therapy ◽

Targeted Therapies ◽

Objective Response ◽

Nucleoside Analogs ◽

Progression Free Survival ◽

Hematological Toxicity ◽

Grade 3

2572 Background: Combining novel targeted therapies with standard treatment is a common strategy in drug development. The primary aim of this systematic review was to provide a summary of the outcomes from studies combining EGFR targeted therapy (ETT) with standard treatments. Methods: A PubMed (1975-Jan, 2012) and ASCO (2005-2011) abstract database search was performed. Eligible studies were RCTs that compared standard therapies (chemotherapy, radiation therapy, or hormonal therapy) to standard therapy plus an ETT. Efficacy outcomes: overall survival (OS), progression free survival (PFS), objective response rate (ORR) time to progression (TTP), clinical benefit rate (CBR), and toxicity (total and grade 3+) were recorded. If any toxicity was significantly more frequent in one arm it was coded as such. Results: 128 studies (60 manuscripts, 68 abstracts) met criteria. Median study enrolment was 230 patients, with breast, lung, and colorectal cancer as the main tumor sites. ETT, cetuximab (41%), trastuzumab (19%), gefitinib (13%), erlotinib (13%), and lapatinib (16%), was combined with platinums, 5FU, taxanes, nucleoside analogs; hormonal therapy and/or radiation therapy. Refer to the table for efficacy results. Most frequent toxicities (common and grade 3+) in the combined arm were rash, diarrhea, hematological toxicity and fatigue. Conclusions: Despite enthusiasm for combining standard treatments with targeted therapies, we have demonstrated mixed efficacy results, with marginal benefit and worse toxicity. Quality of life (Q of L) was rarely reported. A similar analysis is underway for VEGFR, and mTor inhibitors, but raises the question of how best to approach the question of combination therapy. [Table: see text]

Download Full-text

The anti–PD-1 antibody spartalizumab in combination with dabrafenib and trametinib in advanced BRAF V600–mutant melanoma: Efficacy and safety findings from parts 1 and 2 of the Phase III COMBI-i trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10028 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10028-10028 ◽

Cited By ~ 3

Author(s):

Georgina V. Long ◽

Celeste Lebbe ◽

Victoria Atkinson ◽

Mario Mandalà ◽

Paul D. Nathan ◽

...

Keyword(s):

Targeted Therapy ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Safety Data ◽

Stage Iv ◽

Progression Free Survival ◽

Phase Iii ◽

Efficacy And Safety ◽

Grade 3 ◽

The Impact

10028 Background: Treatment (tx) with checkpoint inhibitors or targeted therapy improves outcomes in patients (pts) with BRAF V600–mutant advanced melanoma; however, many pts subsequently progress and die. Preliminary evidence suggests that targeted therapy may enhance the impact of checkpoint inhibitors and improve efficacy compared with either treatment alone. Methods: COMBI-i is investigating first-line spartalizumab 400 mg every 4 wk + dabrafenib 150 mg twice daily + trametinib 2 mg once daily in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). We report efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort), with a median follow-up of 24.3 mo. Response was assessed per RECIST v1.1. The randomized part 3 is ongoing. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 20 (56%) had stage IV M1c disease and 15 (42%) had elevated lactate dehydrogenase (LDH) levels (≥ upper limit of normal). At the data cutoff (August 19, 2019), tx was ongoing in 10 pts (28%). The confirmed investigator-assessed objective response rate (ORR) was 78% (n = 28), with 16 complete responses (CRs; 44%) and 12 partial responses (33%). Median duration of response (DOR; 10/28 responders with events) was not reached (NR); 24-mo DOR rate was 53.4% (95% CI, 29%-73%). Median progression-free survival (PFS) was 22.7 mo; 24-mo PFS rate was 41.4% (95% CI, 23%-59%). At the cutoff, median overall survival (OS) was NR, with a 24-mo OS rate of 74.1% (95% CI, 56%-86%). In pts with elevated LDH, ORR was 67%, with 4 CRs (27%); median PFS was 10.7 mo (95% CI, 4.6-19.1 mo), and median OS was NR. The estimated 24-mo PFS and OS rates in these pts were 26.7% and 52.5%, respectively. All pts had ≥ 1 tx-related adverse event (TRAEs); 26 (72%) had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs were pyrexia (17%), increased lipase (11%), neutropenia (11%), increased blood creatine phosphokinase (8%), and increased γ-glutamyltransferase (8%). AEs leading to discontinuation of all 3 study drugs occurred in 6 pts (17%). All-causality grade ≥ 3 AEs requiring immunosuppressive medication occurred in 19 pts (53%). One pt died of cardiac arrest that was not considered tx related. Conclusions: The combination of spartalizumab + dabrafenib + trametinib resulted in high ORR and CR rates, with a high frequency of durable responses, including in patients with poor prognostic factors. Clinical trial information: NCT02967692.

Download Full-text

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

Digestive Diseases ◽

10.1159/000480257 ◽

2017 ◽

Vol 35 (6) ◽

pp. 611-617 ◽

Cited By ~ 9

Author(s):

Kazuomi Ueshima ◽

Naoshi Nishida ◽

Masatoshi Kudo

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Sequential Therapy ◽

Advanced Hepatocellular Carcinoma ◽

Open Label ◽

Effective Treatment Option ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

Download Full-text

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02964-x ◽

2021 ◽

Author(s):

Yang Wang ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Objective Response ◽

Progression Free Survival ◽

Meaningful Improvement ◽

Free Survival ◽

Significant Difference ◽

Grade 3 ◽

Doublet Chemotherapy ◽

Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.73.0226 ◽

2017 ◽

Vol 35 (29) ◽

pp. 3315-3321 ◽

Cited By ~ 39

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.

Download Full-text

Endometriumkarzinom: Kombination aus Lenvatinib und Pembrolizumab zeigt Wirksamkeit unabhängig vom Mikrosatellitenstatus

Karger Kompass Onkologie ◽

10.1159/000520861 ◽

2021 ◽

pp. 1-2

Author(s):

Sarah Matz

Keyword(s):

Endometrial Carcinoma ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy Analysis ◽

Duration Of Response ◽

Previously Treated Patients ◽

Previously Treated ◽

Prior Systemic Therapy ◽

Grade 3

Purpose: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. Methods: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. Results: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. Conclusion: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile. Trial registration: ClinicalTrials.gov NCT02501096.

Download Full-text

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11565 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 11565-11565

Author(s):

Scott Schuetze ◽

Michael Rothe ◽

Pam K. Mangat ◽

Liz Garrett-Mayer ◽

Funda Meric-Bernstam ◽

...

Keyword(s):

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

Stage Design ◽

Secondary Endpoints ◽

Grade 3 ◽

Ecog Ps ◽

Stage 1 ◽

Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.1074 ◽

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]

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16567 ◽

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]

Download Full-text