PTEN and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6061-6061
Author(s):  
Alexandre Andre B. A. Da Costa ◽  
Felipe D'Almeida Costa ◽  
Andrea Cruz Ferraz de Oliveira ◽  
Carlos Stecca ◽  
Audrey Oliveira ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Predictive Value ◽  
Performance Status ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Tissue Micro Array ◽  
Ecog Performance Status ◽  
Pten Loss ◽  
Platinum Based Chemotherapy ◽  
Micro Array

6061 Background: Platinum-based chemotherapy in association to cetuximab is the standart first-line treatment for metastatic HNSCC. There is no established biomarker for cetuximab efficacy in HNSCC. We have previously shown that PTEN loss of expression is a bad prognostic factor for patients treated with platinum-based chemotherapy and cetuximab. The aim of the present study was evaluate the prognostic impact of PTEN loss of expression in patients treated with or without cetuximab and to evaluate its predictive value to cetuximab benefit. Methods: One hundred and nineteen patients with metastatic or locally recurrent HNSCC were included. Clinical data on treatment and outcomes was retroespectively colected from medical charts. Tissue micro-array was constructed to evaluate PTEN protein expression through immunohistochemistry. Citoplasmatic staining was evaluated using H-score. Tumors with H-score < 10 were considered to present PTEN loss of expression. Results: From the 119 patients 72 were treated with chemotherapy plus cetuximab while 47 were treated with chemotherapy alone. Median overall survival (mOS) was 9.2 months and median progression free survival (PFS) was 4.6 months. Patients treated with cetuximab compared to those who were not treated with cetuximab had a mOS of 11.4 vs 7.0 months (p = 0.770) and a median PFS of 6.2 vs 3.0 months (p = 0.249). Patients with PTEN loss of expression had a worse OS and PFS with mOS of 5.8 vs 10.5 months (p = 0.002) months and mPFS of 3.2 vs 5.2 (p = 0.015). On multivariate analysis including PTEN loss of expression and ECOG performance status both remained independently associated to survival with HR 2.25 (CI95% 1.28-3.97, p = 0.005) for PTEN loss of expression and a HR 1.63 (CI95% 1.07-2.50, p = 0.023) for ECOG. Negative prognostic impact of PTEN loss of expression was seen only in the cetuximab treated patients (mOS 7.3 vs 13.0 months; p = 0.002) but not in the chemotherapy only group (mOS 3.2 vs 7.5 months; p = 0.051). Interaction test for treatment group and PTEN loss of expression showed a p = 0.418. Conclusions: The present study confirms PTEN as a prognostic factor for metastatic HNSCC and suggests PTEN expression should be studied in larger cohorts to evaluate its predictive value to cetuximab response.

The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 415-415
Author(s):  
Husam Alqaisi ◽  
Zachary William Neil Veitch ◽  
Carlos Stecca ◽  
Jeenan Kaiser ◽  
Scott A. North ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
First Line ◽  
Ecog Performance Status ◽  
Cancer Centre ◽  
Platinum Based Chemotherapy ◽  
Line Setting

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p<0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Biomarker-based phase II study of sapanisertib (TAK-228), an mTORC1/2 inhibitor in patients with refractory metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 306-306
Author(s):  
Bradley Alexander McGregor ◽  
Elio Adib ◽  
Wanling Xie ◽  
Walter Michael Stadler ◽  
Yousef Zakharia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Antitumour Activity ◽  
Performance Status ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Additional Treatment ◽  
Mtor Pathway ◽  
Ecog Performance Status ◽  
Pten Loss ◽  
Prior Therapy

306 Background: Approved rapalogs inhibit mTORC1 and have limited activity in mRCC, possibly due to compensatory feedback loops. Sapanisertib addresses the incomplete inhibition of the mTOR pathway through targeting of both mTORC1 and mTORC2 with antitumour activity demonstrated in patients with mRCC. In this multicenter, single arm phase II trial, we evaluated the efficacy of sapanisertib in patients with mRCC progressing on standard therapies (NCT03097328). Methods: Eligible mRCC patients had an ECOG performance status of 0-2 and had progressed on standard therapies. Prior therapy with rapalogs (everolimus, temsirolimus) and variant RCC histologies were permitted. Patients had a baseline biopsy and received treatment with sapanisertib 30 mg by mouth weekly until unacceptable toxicity or disease progression. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Tissue biomarkers of mTOR pathway activation were explored. Results: We enrolled 38 mRCC patients (clear cell = 28; variant histology = 10) between August 2017 and November 2019. The majority had intermediate (76%) or poor risk (11%) by IMDC criteria. Twenty (53%) had received ≥ 3 lines of therapy; 13 (34%) patients received prior rapalogs. Median follow-up was 10.4 months (range 1-27.4) and median duration of therapy was 1.6 (range 0.3-13.8) months. ORR by central review was 2 of 38 (5.3% 90%CI: 1%-15.6%). 31.6% of all patients and 30.7% of those with prior rapalog exposure had some tumor shrinkage during course of treatment. Median progression free survival (PFS) was 2.5 months (95% CI 1.8,3.7). Twelve patients (32%) developed treatment-related grade 3 adverse events (AEs) with no grade 4 or 5 toxicity reported; 6 patients (16%) required dose reduction and 4 (11%) discontinued therapy for AEs. Oncopanel tumor sequencing identified alterations in the mTOR pathway in 6 of 29 patients ( MTOR n = 2, PTEN n = 3, TSC1 n = 1.) Reduced PTEN expression by immunohistochemistry was seen in 7 of 19 patients. There was no association between mTOR pathway mutations or PTEN loss and response to sapanisertib. Conclusions: In this study we demonstrate minimal activity of sapanisertib in patients with treatment refractory mRCC with no clear benefit among patients with mTOR/PTEN pathway alterations. Additional treatment strategies are needed for patients with refractory mRCC.

Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8028-8028
Author(s):  
R. Jotte ◽  
P. Conkling ◽  
C. Reynolds ◽  
L. Klein ◽  
J. F. Fitzgibbons ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2nd-line ED-SCLC sensitive to 1st-line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1st-line platinum-based chemotherapy (recurrence or progression ≥90 days from 1st-line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m2/d (d, 1–3) or IV topotecan 1.5 mg/m2/d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p<0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2nd-line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]

A randomized double-blind phase II study of the Seneca Valley virus (NTX-010) versus placebo for patients with extensive stage SCLC (ES-SCLC) who were stable or responding after at least four cycles of platinum-based chemotherapy: Alliance (NCCTG) N0923 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7509-7509 ◽  
Author(s):  
Julian R. Molina ◽  
Sumithra J. Mandrekar ◽  
Grace K. Dy ◽  
Marie-Christine Aubry ◽  
Katie L Allen Ziegler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Neutralizing Antibodies ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Platinum Based Chemotherapy ◽  
Extensive Stage ◽  
Central Pathology

7509 Background: NTX-010 is a naturally occurring replication-competent picornavirus with potent and selective tropism for SCLC tumor cells expressing neuroendocrine markers. A phase I study of NTX-010 showed evidence of antitumor activity in patients with SCLC. Methods: ES-SCLC patients (pts) with SD, PR or CR after at least 4 cycles of platinum-based chemotherapy were pre-registered to confirm diagnosis of SCLC with > 1 neuroendocrine marker by a central pathology review. Eligible pts were.randomized 1:1 to placebo (B) or NTX-010 (A). NTX-010 or placebo was administered intravenously as a 1-hour infusion in 100 mL normal saline as a single dose of 1 x1011vp/kg. Viral studies to determine distribution, clearance of the virus and the presence of neutralizing antibodies were done. The primary goal of this trial was to compare the progression-free survival (PFS) of arm A to B based on a sample size of 45 patients per arm to detect an improvement in median PFS from 3 to 5 months (m). A pre-planned interim futility analysis was done after 40 PFS events, and reported here. Results: The trial is permanently closed to accrual. One-hundred and twenty pts were pre-registered, of whom 58 were randomized. Baseline age, gender, ECOG performance status, and histology were balanced between arms. Median age was 63 (range: 44 - 82). 31% of pts had a PS of 0 and 69% of 1. Grade 4 adverse events were seen in 3 (12.5%) patients in arm A and none in arm B. Based on the interim futility analysis, PFS was 1.7 m (95% CI: 1.3-3.1) for arm A and 1.7 m (95% CI: 1.4-4.3) for arm B. Pts with viral RNA at 7 (7 pts) and 14 (6 pts) days had worse PFS compared to those with no detectable levels within arm A (1.0 vs 1.6 m, p=0.02; 0.9 vs. 1.2 m, p=0.06). Median follow-up in pts is 6.1 m. The 3-month OS estimates are 83% (95% CI: 69%-100%) and 85% (70%-100%) for arms A and B respectively. Conclusions: This phase II study showed no benefit in PFS for ES-SCLC patients receiving NTX-010. Pts with detectable virus at 7 and 14 days had worse PFS. Clinical trial information: NCT01017601.

Predictive value of BRCA1, ERCC1, ATP7B, PKM2, TOPO-I, TOPO-iia, TOPO-iib, and c-MYC genes in patients with small cell lung cancer (SCLC) who received first-line therapy with cisplatin and etoposide.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7594-7594
Author(s):  
Chara Papadaki ◽  
Niki Karachaliou ◽  
Eleni Lagoudaki ◽  
Maria Trypaki ◽  
Maria Sfakianaki ◽  
...  
Keyword(s):  
Predictive Value ◽  
Performance Status ◽  
Progression Free Survival ◽  
University Hospital ◽  
Integrated Analysis ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Free Survival ◽  
First Line Therapy ◽  
The University

7594 Background: to evaluate the predictive value of genes correlated with cisplatin-etoposide (EP) metabolism or mode of function in patients with SCLC. Methods: Tumor samples from 184 patients, with SCLC were analyzed for ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, TOPOIIB PKM2 and C-MYC mRNA expression by quantitative real-time PCR, from microdissected cells derived from patients’ primary tumors. All patients were treated with EP (plus radiotherapy for patients with limited disease-LS) in the department of Medical Oncology of the University Hospital of Heraklion. Results: The median age of the patients was 63 years (min-max: 33-78). One hundred-twenty (65%) patients presented with extended stage (ES), LDH was above the UNL in 75 (41%), while ECOG performance status was 0-1 in 131 (71%) of them. Shorter progression free survival (PFS) was observed in patients with LS-SCLC whose tumors expressed high ERCC1 (p=0.028), PKM2 (p=0.046), TOPO-I (p=0.008), TOPO-IIA (p=0.002) and TOPO-IIB (p<0.001) expression. High expression of ERCC1 (p=0.014), PKM2 (p=0.026), TOPO-IIA (p=0.021) and TOPO-IIB (p=0.019) was correlated with shortened median overall survival (OS) in LS-SCLC patients. In patients with ES-SCLC, only high TOPO-IIB expression was associated with decreased OS (p=0.035). The favorable genotype (low expression of ERCC1, PKM2, TOPO-IIA and TOPO-IIB) was correlated with significantly improved PFS in both LS-SCLC (p<0.001) and ES-SCLC (p=0.007) patients as well as with improved OS in the LS-SCLC (p=0.007) and ES-SCLC (p=0.011) group. Unfavorable genotype was independent predictor of poor PFS (HR: 3.18; p=0.002) and OS (HR: 4.35; p=0.001) in LS-SCLC as well as for both PFS (HR: 3.14; p=0.021) and OS (HR: 3.32; p=0.019) in ES-SCLC. Conclusions: Single gene’s expression analysis as well as the integrated analysis of ERCC1, PKM2, TOPO-IIA and TOPO-IIB may predict treatment outcome in patients with SCLC. The results of our study, if validated prospectively, may help in selecting patients for personalized therapeutic strategies.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 71-71
Author(s):  
Azim Jalali ◽  
Hui-Li Wong ◽  
Rachel Wong ◽  
Margaret Lee ◽  
Lucy Gately ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Febrile Neutropenia ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Number Of Patients

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

scholarly journals Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Florence Chamberlain ◽  
Sheima Farag ◽  
Constance Williams-Sharkey ◽  
Cecilia Collingwood ◽  
Lucia Chen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Individual Risk ◽  
Duration Of Treatment ◽  
Ecog Performance Status ◽  
Third Line ◽  
Grade 3 ◽  
Dose Reductions

Abstract Background Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Methods Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Results Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. Conclusion Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

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