Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9514-9514 ◽  
Author(s):  
Xiuning Le ◽  
Jonathan Wade Goldman ◽  
Jeffrey Melson Clarke ◽  
Nishan Tchekmedyian ◽  
Zofia Piotrowska ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Dose Intensity ◽  
Continuous Treatment ◽  
Previously Treated ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Dose Reductions

9514 Background: Treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations is an unmet medical need. Poziotinib is a potent tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 insertion mutants. We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations in an independent cohort of a multi-cohort, multi-center Phase 2 study ( ZENITH20-1). Methods: ZENITH20-1 study enrolled pts with advanced NSCLC with an EGFR exon 20 insertion identified on local tissue testing who had received at least one prior line of therapy. Poziotinib (16 mg) was administered orally QD, allowing dose reductions for AEs, with follow up for 24 months. The primary endpoint was objective response rate (ORR), evaluated centrally by RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety. Efficacy was also evaluated by specific exon 20 insertions and prior lines of therapy. Results: 115 patients with a median age of 61 years (33-83) were enrolled. Patients had a median of 2 prior lines of therapy (range, 1-9.) The median relative dose intensity was 72% (7-100%) with 65% having dose reductions. The ORR in the as-treated population was 14.8% (95% CI 8.9 - 22.6%), and the DCR was 68.7% (95% CI 59.4 - 77.0%) with a median DoR of 7.4 months. 65% patients had tumor size reductions and the median PFS was 4.2 months. In the evaluable population (n = 88), the ORR was 19.3% and the unconfirmed ORR was 25%. Responses were predominantly observed in insertions between residues M766 to D770 of exon 20 (8/44; 18.2%). Responses were observed in patients with 2 lines (14%); ≥3 lines of therapy (16.2%). The most common treatment-related Grade ≥3 AEs were rash (28%), diarrhea (26%), stomatitis (9%) and paronychia (6%). The incidence of treatment-related pneumonitis was 4%, however some cases may have been confounded by prior checkpoint inhibitors as first line treatment. Conclusions: Although the ORR primary endpoint was not met, poziotinib induced tumor reduction in the majority of patients with durable responses, including the heavily pre-treated population. Responses were more common in patients with insertions between M766 to D770 of EGFR exon 20. The safety profile was overall consistent with other 2nd generation EGFR TKIs. Evaluation of these subgroups with refined dosing and improved toxicity management to maintain continuous treatment is warranted to assess the potential of poziotinib in Exon20 related tumors. Clinical trial information: NCT03318939 .

Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA1010-LBA1010 ◽  
Author(s):  
J. Bergh ◽  
R. Greil ◽  
N. Voytko ◽  
A. Makhson ◽  
J. Cortes ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Recommended Treatment

LBA1010 Background: Taxane-based chemotherapy (CT) improves progression-free survival (PFS) in patients (pts) with newly diagnosed HER2-negative metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor (MTKI), demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC. A randomized, open-label, multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone. Methods: Eligible pts (female; ≥18 yrs) had an ECOG PS ≤1, and newly diagnosed HER2-negative MBC or ABC. If (neo)adjuvant therapy included a taxane, relapse must have occurred ≥12 mos after CT. Pts were randomized (1:1) to treatment (tx) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2–15 q3w (Schedule 2/1; Arm A), or to D 100 mg/m2 iv 1-hr infusion q3w (Arm B) that could be given until progression. If D was discontinued in Arm A for reasons other than progressive disease (PD), single-agent SU 37.5 mg daily was permitted until PD. Median, independently assessed, PFS (primary endpoint) was compared between tx arms using stratified and unstratified log-rank tests. Overall objective response rate (ORR), overall survival (OS), pt-reported outcomes, and safety were secondary endpoints. Results: As of the data cutoff (February 1, 2010), the ITT population comprised 593 pts (SU+D, n=296; D, n=297). The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS. Baseline characteristics were well balanced. Median relative dose intensity (RDI) was 94.2% and 92.4% for SU+D, and 92.6% for D arms, respectively. Median PFS was 8.6 mos (95% CI 8.2–10.3) in the SU+D arm vs 8.3 mos (95% CI 7.7–9.6) for the D arm (HR 0.922). Median OS was 24.8 mos (95% CI 21.5–33.1) in SU+D arm vs 25.5 mos (95% CI 22.8–27.8) for D arm (HR 1.207). ORR was significantly better for SU+D (51%) vs. D (39%) (p=0.0018). Frequent all causality grade 3/4 adverse events (≥10%) were neutropenia (46%), hand–foot syndrome (17%), and fatigue (12%) in the SU+D arm and neutropenia (44%) in the D arm. Conclusions: Based on these data, SU+D is not a recommended treatment option for patients with newly diagnosed ABC. Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited. [Table: see text]

Phase II study of brigatinib in ROS1 positive non-small cell lung cancer (NSCLC) patients previously treated with crizotinib: Barossa cohort 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9040-9040
Author(s):  
Haruko Daga ◽  
Seiji Niho ◽  
Jun Sakakibara-Konishi ◽  
Hiroshi Tanaka ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Independent Review ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps ◽  
Nsclc Patients ◽  
Age Range

9040 Background: Brigatinib is a next-generation tyrosine kinase inhibitor targeting ALK and ROS1. Crizotinib is the first drug approved for the treatment of ROS1 fusion-positive NSCLC. Standard treatment for crizotinib-resistant ROS1 positive NSCLC is not established. Barossa is a multicenter, phase II basket, study of brigatinib in patients with ROS1 positive solid tumors. This study is composed of three cohorts. ROS1 inhibitor-naïve ROS1 positive NSCLC patients were enrolled in the cohort 1, and ROS1 positive NSCLC patients previously treated with crizotinib were enrolled in the cohort 2. Patients with ROS 1 positive solid tumors other than NSCLC were enrolled in the cohort 3. This time we report the cohort 2 results. Methods: Patients with advanced, previously treated with crizotinib, ROS1 positive NSCLC received brigatinib at a dose of 180 mg once daily with a 7-day lead-in period at 90 mg. The primary end point was objective response rate (ORR; RECIST 1.1) by independent review. Key secondary endpoint was PFS, OS, and safety. The sample size was set at 19 patients, with a one-sided alpha of 0.05, beta of 0.2, and threshold and expected values for primary endpoint of 20% and 50%, respectively. Results: From July 2019 and Jan 2020, 19 patients were enrolled from 9 institutions. Baseline characteristics as follows: median age (range): 60 (31-75) years; women, n = 10 (53%); ECOG PS of 0 to 1, n = 18 (95%); never smoker, n = 11 (58%); tumor histopathological type: adenocarcinoma, n = 18 (95%). Five and 6 patients achieved PR and SD, respectively at data cutoff date of 30 Oct 2020. The ORR was 26.3% (90%CI, 11.0-47.6), and the disease control rate was 57.9% (95%CI, 33.5-79.7). The median duration of follow-up for PFS was 12.0 months. The median PFS was 7.3 months (95% CI, 1.3-9.3), and the 1-year PFS rate was 26.9% (95%CI, 9.2-48.6). Grade ≥3 TRAEs were CPK increased (21.1%), infection (5.3%), AST and/or ALT increased (5.3%), hypercalcemia (5.3%), anorexia (5.3%), hypoxia (5.3%), erythema (5.3%), hypertension (5.3%). Pneumonitis was observed in one patient (5.3%, Grade 2). No treatment-related death was observed. Conclusions: Brigatinib has modest activity for ROS1 positive NSCLC patients previously treated with crizotinib. The safety profile of brigatinib was consistent with previous studies. Enrollment of the cohort 1 for ROS1 inhibitor-naïve NSCLC patients is ongoing, and the data will be presented at a future congress. Clinical trial information: JapicCTI-194851.

scholarly journals Dissociated Response and Clinical Impact in Patients Treated With Nivolumab Monotherapy

2020 ◽  
Author(s):  
Yuki Sato ◽  
Takeshi Morimoto ◽  
Shigeo Hara ◽  
Kazuma Nagata ◽  
Kazutaka Hosoya ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Treatment Strategies ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Nsclc Patients

Abstract Background: Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy, and aimed to provide insight on how to potentially improve the management of this group of patients.Methods: We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital.Results: Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (not reached vs. 8.0 months, p = 0.039). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively.Conclusion: DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival. Further research is required to elucidate the characteristics, treatment strategies, and underlying mechanisms of DR in NSCLC patients.

CNS activity of poziotinib in NSCLC with exon 20 insertion mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9093-9093
Author(s):  
Xiuning Le ◽  
Marina Chiara Garassino ◽  
Robin Cornelissen ◽  
Mark A. Socinski ◽  
Nishan Tchekmedyian ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Objective Response ◽  
Survival Rates ◽  
Unmet Need ◽  
Cns Metastases ◽  
Cns Activity ◽  
Previously Treated ◽  
Exon 20 ◽  
Insertion Mutations

9093 Background: Treatment addressing non-small cell lung cancer (NSCLC) harboring EGFR or HER2 exon 20 insertion mutations remains an unmet need. These tumors are associated with a high incidence of CNS metastases and unfavorable survival rates. Poziotinib is a potent, irreversible, tyrosine kinase inhibitor (TKI) with a structure that can overcome the steric hindrance of the exon 20 limited binding pocket. Preclinical data suggest poziotinib CNS penetration, and here we show meaningful poziotinib CNS activity in patients with NSCLC harboring exon 20 insertion mutations in an ongoing multi-cohort, multi-center Phase 2 study (ZENITH20; NCT03318939). Methods: ZENITH20 enrolled previously treated and naïve patients with advanced/metastatic NSCLC and EGFR or HER2 exon 20 insertion mutations in several cohorts: Cohort 1 (C1) EGFR previously treated; Cohort 2 (C2) HER2 previously treated and Cohort 3 (C3) EGFR treatment-naïve. All patients with stable CNS metastases at baseline were included. Poziotinib (16 mg) was administered orally QD, with follow-up for up to 24 months. The primary endpoint was Objective Response Rate (ORR) evaluated centrally using RECIST v1.1 by an independent image review committee. Secondary endpoints included Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS) and safety. Primary efficacy results have been previously released. Intracranial response was determined based on the modified RECIST criteria. Results: A total of 284 patients across 3 cohorts (C1 n=115; and C2 n=90; and C3 n=79) with a median age of 60.5 years were enrolled. The median follow-up was 7.3, 8.3, and 9.2 months for all patients in C1, C2, and C3, respectively. In NSCLC patients that had baseline CNS lesions (N=36), the analysis showed a patient-based ORR of 22.2% (8/36) and a DCR of 88.9% (32/36). One patient in each cohort had a complete intracranial response and stable disease was 80.6% across 3 cohorts and 92.9% in C2. Two patients each in C1 and C3 had progressive disease (PD) and none had CNS progression in C2 (Table). Conclusions: Poziotinib exhibited clinically meaningful CNS activity in patients with EGFR or HER2 exon 20 mutations in ZENITH20 Cohorts 1-3. The majority of the patients had no CNS progression and 3/36 patients had intracranial complete responses. The preliminary data suggest that poziotinib may provide a meaningful treatment alternative for patients with NSCLC that harbor EGFR or HER2 exon 20 mutations and who present with CNS metastases that have poor prognosis. Clinical trial information: NCT03318939. [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.

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

BREAKWATER: Randomized phase 3 study of encorafenib (enco) + cetuximab (cetux) ± chemotherapy for first-line (1L) treatment (tx) of BRAF V600E-mutant (BRAFV600E) metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3619-TPS3619
Author(s):  
Scott Kopetz ◽  
Axel Grothey ◽  
Rona Yaeger ◽  
Fortunato Ciardiello ◽  
Jayesh Desai ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Egfr Inhibitor ◽  
Braf Mutations ◽  
Open Label ◽  
Phase 3 ◽  
Previously Treated

TPS3619 Background: Approximately 10% of patients (pts) with mCRC have BRAF mutations (mostly V600E). 1L tx options for BRAFV600E mCRC are limited to cytotoxic chemotherapy ± anti-VEGF or anti-EGFR, or immune checkpoint inhibitors in pts with MSI-H tumors. In Europe, Japan, and USA, the combination of BRAF inhibitor enco + EGFR inhibitor cetux is approved for tx of BRAFV600E mCRC after prior therapy. In BEACON CRC, enco + cetux resulted in a median overall survival (OS) of 9.3 months (95% confidence interval [CI]: 8.0–11.3) and an objective response rate (ORR) of 19.5% (95% CI: 14.5%–25.4%) in previously treated pts with BRAFV600E mCRC (median follow-up: 12.8 months); 57.4% of pts had grade 3/4 adverse events (AEs); 9% discontinued due to AEs. Given the poor prognosis of pts with BRAFV600E mCRC and based on the efficacy and tolerability of enco + cetux from BEACON CRC, BREAKWATER will evaluate efficacy and safety of enco + cetux ± chemotherapy in tx-naive pts with BRAFV600E mCRC. Methods: BREAKWATER is an open-label, global, multicenter, randomized, phase 3 study with a safety lead-in (SLI). Approximately 60 and 870 pts will be enrolled in the SLI and phase 3 parts of the study, respectively. Pts must have BRAFV600E mCRC (determined using tumor tissue or blood); ECOG performance status 0/1; and adequate bone marrow, hepatic, and renal function. Pts in the SLI must have evaluable disease (RECIST v1.1) and have received ≤ 1 prior tx regimen; those previously treated with a BRAF or EGFR inhibitor, or both oxaliplatin and irinotecan, will be excluded. Pts in the phase 3 study must have measurable disease and be tx naive for metastatic disease. Study tx and endpoints are shown in the table. Enrollment began on 6 January 2021. Clinical trial information: NCT04607421. [Table: see text]

Phase I/II trial of pembrolizumab and cabozantinib in the treatment of metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4544-4544
Author(s):  
Elizabeth R Kessler ◽  
Junxiao Hu ◽  
Geetika Srivastava ◽  
Douglas Jerome Kemme ◽  
Praveena Iruku ◽  
...  
Keyword(s):  
Phase I ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Controlled Trial ◽  
Objective Response ◽  
Risk Category ◽  
Serious Adverse Events ◽  
Line Therapy

4544 Background: Checkpoint inhibitors (CPI) and vascular endothelial growth factor receptor inhibitors (VEGFi) are standard treatments for patients (pts) with mRCC. This phase I/II study evaluated the safety and efficacy of the novel combination of pembrolizumab (pembro) and cabozantinib (cabo). The phase I dose escalation data was presented at ASCO GU 2019. We now report the objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicity of patients in the phase II dose expansion. Methods: Eligible pts had metastatic clear cell (ccRCC) or non-clear cell (nccRCC) histology, normal organ function, ECOG 0-1, and no prior exposure to pembro or cabo. Pts could be treatment-naïve or have received prior CPI and/or VEGFi. Pts were dosed at the recommended phase 2 dose of pembro 200 mg IV Q3W in combination with cabo 60 mg PO QD. Scans were obtained every 9 weeks. Treatment beyond progression, in the setting of continued clinical benefit, was allowed. The primary endpoint was ORR. Simon’s two-stage design was implemented to test the null hypothesis that ORR ≤ 0.20 versus the alternative that ORR ≥ 0.50. Results: Forty pts were enrolled, of which 34 pts (85%) had ccRCC and 6 pts (15%) had nccRCC. This was first-line treatment for 15 pts (38%) and second- and subsequent-line therapy for 25 pts (62%). IDMC risk category was favorable in 15%, intermediate in 72.5%, and poor in 12.5% of pts. Prior therapies included VEGFi in 17 pts (43%), CPI in 17 pts (43%), and 9 pts (23%) had both prior VEGFi and CPI in combination or sequentially. At a median follow up of 17.8 months (mo), the ORR was 60% (95% CI 0.458-1.00), clinical benefit rate (CBR) was 92.5% (95% CI 0.817-1.00), median time to response was 4.2 mo; median duration of response was 8.4 mo. Three of six nccRCC pts achieved partial response. Median PFS was 10.4 mo (95% CI 6.3 mo-NR). Median OS was not reached. Twelve patients remain on treatment. The most common grade 1 and 2 (G1/2) treatment-related AEs were diarrhea (53%), fatigue (49%), weight loss (47%), nausea (43%), and dysgeusia (43%). Twenty-five patients (47%) experienced a treatment-related G3 AE and there were no G4 related AEs. Thirteen pts experienced serious adverse events, 8 of which were related to treatment: G3 transaminitis and hypoglycemia were attributed to the combination; G3 pancreatitis, nephritis, and pneumonitis attributed to pembro; G3 pulmonary embolus, confusion due to reversible posterior leukoencephalopathy (RPLS), and stroke attributed to cabo. There was one treatment-related death in the pt with RPLS, possibly related to cabo. Conclusions: This study of the combination of pembrolizumab 200mg and cabozantinib 60mg met the primary endpoint of ORR. Benefit was seen in first- and subsequent-line therapy. The safety profile was manageable. This combination warrants further confirmation in a randomized controlled trial. Clinical trial information: NCT03149822.

Clinical and molecular characteristics of advanced non-small cell lung cancer (NSCLC) patients (pts) with rapid progressive disease (RPD) on gefitinib therapy (G)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7592-7592
Author(s):  
M. J. Fidler ◽  
L. Buckingham ◽  
M. Gale ◽  
J. Coon ◽  
A. Mauer ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Objective Response ◽  
Gene Copy Number ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Molecular Characteristics ◽  
Kaplan Meier ◽  
G 12 ◽  
Nsclc Patients

7592 Background: Prognostic factors associated with better outcomes (EGFR mutations (mut), high EGFR gene copy number, never smoking) can be used to select pts for EGFR tyrosine kinase inhibitor (TKI) combination trials, but would exclude the majority of NSCLC pts. Excluding pts with the worst likely outcomes is another strategy that may result in more pts who could benefit from the combination of a TKI with other agents. Our objective was to identify clinical and molecular characteristics associated with RPD (=70 days) and shorter progression-free survival (PFS) in previously treated NSCLC pts receiving G. Methods: Consecutive Expanded Access Trial pts with >1 week G were included for analysis. Tissue from 87 pts was evaluated for EGFR, pAKT and PTEN protein expression by immunohistochemistry; 58 tumors were analyzed for mut and sum of CA dinucliotide repeats (ΣCA rpts) by SSCP, PCR and sequencing. Results: There were 150 pts; 77 female, median (md) age 67. Md follow-up was 5.8 months (mo). Objective response was 8% (2CR, 10PR, 56 SD, 82 RPD). Md Kaplan-Meier PFS and survival were 2.0 and 5.8 mo, respectively. See table for univariate results. Smoking, Mut-PTEN-, EGFR-PTEN- and EGFR-pAKT- tumors were associated with shorter PFS. Separate clinical and molecular multivariate models were developed. In logistic regressions, non-adenocarcinoma histology (N- A), p=0.004, =12 mo from diagnosis to G (dx-G =12 mo), p=0.0009, lack of mut (p=0.0298) and ΣCA rpts <34 (p=0.0622) were associated with RPD. In Cox regressions, N-A (p=0.0256), dx-G =12 mo (p=0.0166) and lack of mut (p=0.0298) were associated with shorter PFS. Conclusions: N-A, dx-G =12 mo and lack of mut were associated with RPD and shorter PFS in univariate and multivariate analyses. ΣCA rpts <34 and double-negative molecular combinations were also related to worse outcome. These clinical and molecular characteristics may warrant further study as exclusion criteria for TKI combination clinical trials. [Table: see text] [Table: see text]

Phase II study of capecitabine (X) as palliative treatment for patients (p) with squamous head and neck cancer (HNC) with locoregional and/or metastatic relapse after previous platinum-based treatment (PBT): An interim analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6074-6074
Author(s):  
J. Martínez-Trufero ◽  
D. Isla ◽  
J. C. Adansa ◽  
R. Hitt ◽  
J. J. Cruz
Keyword(s):  
Palliative Treatment ◽  
Lung Metastases ◽  
Treatment Options ◽  
Objective Response ◽  
Dose Intensity ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Metastatic Relapse ◽  
Previously Treated ◽  
Ecog Ps

6074 Background: PBT is the standard therapy for HNC and is widely used as first line treatment. Nevertheless the incidence of relapse remains still high. Therefore, new non-platinum drugs need to be asses as second line treatment options. Taking into account the results obtained with X in HNC, we proposed this study to evaluate activity and tolerability of X when used as palliative monotherapy for relapsed HNC p previously treated with PBT. Methods: Patients aged 18–75 years, ECOG PS 0–2, with advanced squamous HNC with locoregional and/or metastatic relapse previously treated with PBT and adequate bone marrow, renal and hepatic functions were included. X (1,250 mg/m2 BID) during 14 days was administered every 21 days, for at least 2 cycles. Objective response rate (ORR) was assessed according RECIST criteria and toxicity following NCI-CTC v2 criteria. Results: Sixteen patients with median age 57 years old, all of them male, ECOG 0/1 (33.3% / 66.7%) and with squamous HNC, were analyzed. Twelve p had local disease, 4 p adenopathies and 6 p lung metastases. Median time since HNC diagnosis was 30.4 months and since disease extension diagnosis, 1.8 months. All p received a total of 58 cycles of X (median 3, range 1–6) and the median relative dose intensity was 92%. Four p were not evaluable for response (1 is still on treatment; 3 died, 2 due to unknown reasons and 1 due to an infection). ORR was 16.7%.The median follow-up time was 3.3 months, median TTP was 4.2 months and median OS was 4.7 months. Hematological toxicity G3/4 was reported in 2 p. The only grade 4 non-hematological toxicity was dysphagia in 1 p; grade III toxicities were: asthenia (2 p), anorexia (1 p), dehydratation (1 p), diarrhea (1 p), mucositis (1 p), weight loss (1 p) and palmar-plantar erythrodysesthesia (1 p). The most common grade II toxicity was asthenia (2 p). Conclusions: Capecitabine seems to be an active, feasible and well tolerated palliative treatment for advanced HNC patients that have previously received platinum-based schedules. No significant financial relationships to disclose.

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