Intratumoral injection of oncolytic adenovirus H101 in combination with vinorelbine/cisplatin chemotherapy in patients with advanced non-small cell lung cancer

17082 Background: Chemotherapy is main treatment for advanced NSCLC. But its efficacy is quite small with improvement of 1–2 months in median survival. New strategy against NSCLC is needed. Oncolytic adenovirus H101 is found to be effective against NSCLC. This trial is desigened to investigate efficacy and toxicity of intratumoral injection of H101 in combination with chemotherapy in the treatment of NSCLC. Methods: The NSCLC patients confirmed cytologically or pathologically were randomized to intratumoral injection of adenovirus H101 (1.5 × 1012 viral particles) plus NP chemotherapy (arm A) or NP chemotherapy (arm B). Objetive response was evaluated every two cycles and time to progression (TTP) and overall survival were followed up. Results: Out of 18 evaluable patients in Arm A, 4 patients showed partial response (PR),3 minor response(MR), 7 stable disease (SD) and 4 disease progression (PD), while in Arm B 16 evaluable patients showed 3 PR, 4 MR, 3 SD and 6 PD. At the first time of response evaluation, there was 1 PD in Arm A,but in Arm B there were 5 of PD. Failure rate in Arm B was significantly higher than in Arm B. Survival curves between the two arms were similar. Six month, 9 month and 1 year survival rates were slightly higher in Arm B and median TTP was also prolonged in Arm A. Except non-infectious fever, Arm A was similar in other toxicities to Arm B. there was only 2 patients developing mild pneumothorax. Conclusions: Intratumoral injection of H101 1.5 × 1012 viral particles in combination with NP chemotherapy was feasible, effective and safe in treatment of advanced NSCLC. No significant financial relationships to disclose.

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CGTG-102 (Ad5/3-D24-GMCSF), a novel oncolytic adenovirus, in patients with refractory solid tumors: Experience from an advanced therapy access program.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e13035 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e13035-e13035

Author(s):

Mikael Von Euler ◽

Anna Kanerva ◽

Petri Nokisalmi ◽

Anniina Koski ◽

Iulia Diaconu ◽

...

Keyword(s):

Solid Tumors ◽

Oncolytic Adenovirus ◽

Eligibility Criteria ◽

Minor Response ◽

Preclinical Testing ◽

Viral Particles ◽

Advanced Therapy ◽

Wide Range ◽

Major Organ ◽

Tumor Types

e13035 Background: Following preclinical testing CGTG-102, a 5/3 chimeric oncolytic adenovirus armed with human GMCSF, has been used to treat 115 refractory cancer patients. Methods: Eligibility criteria included refractory advanced solid tumors, no major organ deficiencies and written informed consent. Patients were treated with either a single treatment or serial treatments with one or more viruses. Intra tumoral administration was performed under ultrasound guidance. The initial dose, 8 x 1010 Viral Particles (VP), was based on published safety results and preclinical testing and escalated in later patients. A routinely tolerated dose of 3 x 1011 VP was deemed optimal and is the target dose for clinical development. To reduce regulatory T-cells, low-dose cyclophosphamide 50 mg/day was given. Adverse Reactions (AR) were scored according to CTCAE 3.0. Imaging was done by CT before and ~2 months after treatment. Response was scored according to RECIST 1.1, including injected and non-injected lesions. Decrease not fulfilling PR was scored as minor response (MR). Results: The most common ARs were pain (82%), fever (81%), fatigue (79%), nausea (54%) and hemoglobin decrease (48%). Pain is mostly tumor pain or pain in the injected tumor, which may be causally related to the MOA of the therapy. Most ARs were G1 or G2; 6 were G4: 2 Hb decrease, 2 pulmonary embolism and single reports of thrombocytopenia and pericardial effusion, most probably due to the underlying disease.Imaging was performed when clinically useful. 65/115 are evaluable by imaging: 3% PR, 11% MR, 40% SD and 46% PD. Best results were obtained in Breast Cancer, Melanoma, Soft Tissue Sarcoma, Mesothelioma and Ovarian Cancer. Median survival in this heavily pre-treated refractory population is 164d, 95% CI 122d – 206d. Mean survival is 281d reflecting that approx. 30% survive more than 300d and 15% up to 600d. A wide range of samples are being analyzed to further characterize the viral and immunological aspects of the therapy. Conclusions: CGTG-102 is a novel oncolytic adenovirus with good safety profile and encouraging signs of efficacy. Formal clinical studies are underway in several tumor types in both US and EU.

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A randomized phase III trial of single-agent pemetrexed (P) versus carboplatin and pemetrexed (CP) in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7506 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7506-7506 ◽

Cited By ~ 13

Author(s):

Rogerio Lilenbaum ◽

Mauro Zukin ◽

Jose Rodrigues Pereira ◽

Carlos H. Barrios ◽

Ronaldo De Albuquerque Ribeiro ◽

...

Keyword(s):

Combination Chemotherapy ◽

Advanced Nsclc ◽

Performance Status ◽

Single Agent ◽

Survival Rates ◽

Standard Of Care ◽

Patient Characteristics ◽

Phase Iii ◽

And Performance ◽

Nsclc Patients

7506 Background: No standard of care exists for patients with advanced NSCLC and PS 2 and clinical practice ranges from supportive care to combination chemotherapy. Methods: In a Brazilian multicenter phase III randomized trial, advanced NSCLC patients, with any histology at first, amended to non-squamous only, PS 2, no prior chemotherapy, and adequate organ function, were randomized to P alone (500 mg/m2) or CP (AUC 5 + same P) administered every 3 weeks for 4 cycles. Stratification factors included stage (IIIB vs. IV); age (≥70 vs. <70); and weight loss (≥5 kg vs. <5kg). The primary endpoint was overall survival and the study was powered to demonstrate an improvement in median survival from 2.9 to 4.3 months based on a prior CALGB trial. Results: A total of 217 patients were enrolled from 8 centers in Brazil and 1 in the US from April 2008 to July 2011. Twelve patients were ineligible and excluded. The 2 arms (P=102; CP=103) were balanced for patient characteristics. 14 patients had squamous and another 12 had unknown histology. The response rates were P = 10% and CP = 24% (p=0.019). In the ITT population, the median PFS was P = 3.0 mo and CP = 5.9 mo (HR=0.46, 95% CI 0.34; 0.63, p<0.001) and median OS was P = 5.6 mo vs. CP = 9.1 mo (HR=0.57, 95% CI 0.41; 0.79, p=0.001). 1-year survival rates were 22% and 39% respectively. Similar results were seen when squamous patients were excluded from the analysis. Grade ¾ anemia (5.5%; 12%) and neutropenia (2.8%; 5.6%) were more frequent in CP. There were 4 treatment-related deaths in the CP arm. 30% of patients in each arm received 2nd line therapy Conclusions: Combination chemotherapy with CP significantly improves survival, with acceptable safety, in eligible patients with advanced NSCLC and PS 2, and represents a new standard.

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Pembrolizumab Alone or Combined With Chemotherapy in Advanced NSCLC With PD-L1 ≥50%: Results of a Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.691519 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ya Chen ◽

Yanan Wang ◽

Zhengyu Yang ◽

Minjuan Hu ◽

Yanwei Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Survival Rates ◽

Progression Free Survival ◽

Standard Of Care ◽

Programmed Death ◽

Platinum Based Chemotherapy ◽

Prospective Trials ◽

Nsclc Patients

ObjectivesPembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy (PM) both become standard of care in patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50%. This study aimed to figure out the better treatment choice.MethodIn this retrospective analysis, we compared the clinical efficacy of PM and PC as first-line treatment in NSCLC patients with a PD-L1 ≥50% and negative for genomic alterations in the EGFR and ALK genes.ResultAmong the population, 115 patients received PC, and 91 patients received PM. Up to Dec 30, 2020, median follow-up was 17.13 months. The median progression-free survival (PFS) rates of PC and PM were 12.37 and 9.60 months (HR: 0.44, p < 0.001), respectively. The median overall survival (OS) rates were NE and 28.91 months (HR: 0.40, p = 0.005), respectively. Subgroup analysis found that the PFS benefit of PC was evident in most subgroups excepting patients with brain metastasis. The 1-year overall survival rates of PC and PM were 89.3% and 76.1%, respectively. The ORR was 61.7 and 46.9% (p = 0.004), respectively.ConclusionIn patients with previously untreated, PD-L1 ≥50%, advanced NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard platinum-based chemotherapy seems to be the preferred treatment, which needs to be validated by further prospective trials.

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A randomized, phase II trial comparing sequential paclitaxel/cisplatin/gemcitabine/vinorelbine/ (PCGV) with cisplatin/gemcitabine/vinorelbine/ (CGV) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17008 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17008-17008

Author(s):

J. De Castro ◽

C. Belda-Iniesta ◽

E. Casado Saenz ◽

J. Feliu ◽

M. Sereno ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Phase Ii ◽

Advanced Nsclc ◽

Rank Test ◽

Time To Progression ◽

Who Grade ◽

Log Rank Test ◽

Randomized Phase Ii ◽

Grade 3 ◽

Nsclc Patients

17008 Background: New effective therapies are needed to improve the outcome of patients with advanced NSCLC. In this regard, new approaches such as cisplatin-based triplets have been explored with promising results but high toxicity. Furthermore, sequential chemotherapy schedules with taxanes followed by cisplatin-based regimens or viceversa could improve activity. A phase II study showed that sequential chemotherapy with weekly paclitaxel followed by CGV was highly active. Methods: A multicenter, randomized phase II trial of PCGV vs CGV in advanced NSCLC patients was conducted. Primary end-point: time to progression and survival. Eligible pts had unresectable, histologically confirmed NSCLC; no prior chemotherapy; PS 0–2; measurable disease. Pts received: Arm A (PCGV): P 150 mg /m2/week × 6, followed 2 weeks later by C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Arm B (CGV): C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Results: 106 Pts were included. Pts baseline characteristics (A/B: 52/54): male 82/79%; median age 60/59 (range 38–75 years); PS 0: 30/33%; 1 63/60%; 2: 7/7%; % squamous carcinoma:44/42%.WHO grade 3–4 toxicities for P were: neutropenia 18%; anemia 10%; thrombocytopenia 2%, peripheral neuropathy 18%. Grade 3–4 toxicities for CGV after P were: neutropenia 31%,nausea-vomiting 20%,thrombocytopenia 7%,anemia 5%,peripheral neuropathy 21%. WHO grade 3–4 toxicities for arm B were: neutropenia 35%,nausea-vomiting 19%, anemia 12%, thrombocytopenia 11% and peripheral neuropathy 15%. After therapy with arm A, 44% achieved a partial response, 15% had stabilization and 41% progressed. Arm B response rate were as follows: partial response 33%, stable disease 24% and progressive disease 43%. Median time to progression was (A/B) 7/6 months (log rank test, p 0.13) and median survival was (A/B): 11/10 months (log rank test, p 0.5). Conclusions: In spite of high response rate in TCGV arm, no survival benefit was detected in advanced NSCLC patients. No significant financial relationships to disclose.

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Survival versus intrinsic and acquired resistance in advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19066 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19066-e19066 ◽

Cited By ~ 1

Author(s):

David J. Stewart ◽

Pierre Saintigny ◽

Glenwood D. Goss ◽

Charles Lu

Keyword(s):

Progressive Disease ◽

Advanced Nsclc ◽

Acquired Resistance ◽

Resistance Pattern ◽

Time To Progression ◽

Incremental Change ◽

Clinical Resistance ◽

Resistance Patterns ◽

Nsclc Patients ◽

Serial Measurements

e19066 Background: While advanced NSCLC responds to platinum-based therapy (PBT), intrinsic and acquired resistance limits efficacy. We assessed impact of resistance patterns on overall survival (OS). Methods: Using serial measurements of tumor diameters from 130 NSCLC patients on PBT, we calculated % incremental change in tumor size compared to the most recent prior scan and % overall change from pre PBT. Results: 98/130 (75%) had measurable tumor shrinkage (TS) at 1st repeat scan (RS) post 2 cycles, of whom 81 had a 2nd RS post 4 cycles. Of these, 20 (25%) had tumor growth (TG) at the 2nd RS. Only 1 had initial TG then followed by TS. Of 41 with a 3rd RS <4 weeks post cycle 6, 13/41 (32%) had TG. The greatest % incremental TS (compared to most recent prior scan) was seen early (at 1st RS) for 76% of patients. Rate of TS decreased with later cycles in these patients. 11 patients had rapid TS on 1st RS, then gradual further shrinkage over >3 subsequent scans, while 15 had progressive gradual TS over >4 scans without initial rapid TS. By Spearman coefficients, maximum % TS from pre PBT over all scans correlated with OS (r=0.46, p<0.0001), time to progression (TTP) (r=0.69, p<0.0001) and post-progression survival (PPS) (r=0.30, p=0.001). TTP also correlated with OS (r=0.63, p<0.0001), TTP correlated with PPS (r=0.44, p<0.0001), and OS correlated with PPS (r=0.95, p<0.0001). Median OS (11.0 months for all patients) varied with TS pattern (p<0.0001): OS for patients with first TG at 1st, 2nd, 3rd and 4th RS was 5.9, 10.8, 10.5 and 15.1 months. OS was 18.2 months in patients with most TS at 1st RS followed by gradual further TS over later scans, and was 30.5 months with progressive gradual TS without rapid TS at 1st RS. OS with RECIST partial response (23% of patients), minor TS (52%), minor TG (13%) and RECIST progressive disease (13%) was 16.9, 12.4, 9.8 and 4.0 months (p<0.0001). Conclusions: OS, TTP and PPS correlate strongly with response (degree of TS/TG) and with resistance pattern. OS is longest with progressive further TS over multiple scans. Within this group, partial acquired resistance (decreased TS rate after initial rapid TS) has shorter OS than with sustained incremental TS. The underlying biological factors driving clinical resistance remain undefined.

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Soluble vascular endothelial growth factor receptor 2 (VEGFR2): New biomarker in advanced non-small cell lung cancer (NSCLC)?

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22108 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22108-e22108 ◽

Cited By ~ 1

Author(s):

E. Sanmartin ◽

E. Jantus Lewintre ◽

R. Sirera ◽

M. Miñana ◽

A. Navarro ◽

...

Keyword(s):

Advanced Nsclc ◽

Growth Factor Receptor ◽

Large Cell ◽

Vascular Endothelial ◽

Time To Progression ◽

Significant Difference ◽

Nsclc Patients ◽

Endothelial Growth Factor ◽

Lower Expression

e22108 Background: An increase in VEGF expression in tumour or some blood compartments (i.e. serum or plasma) has been found in solid tumours of various origins. Several studies have suggested that ligands and receptors of the VEGFs/VEGFR system play an important role in tumour growth and is associated with metastasis and poor prognosis. The aim of our study was to investigate the usefulness of plasmatic VEGFR2 quantification as a new biomarker in advanced NSCLC. Methods: We studied 106 healthy controls (c) and 467 advanced NSCLC patients (p) (stage IIIB and IV) treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy and the plasmatic levels of the VEGFR2 were determined by ELISA. Results: In the NSCLC group, the median age was 59.9, range (31–80); 82% were males. The histological subtypes were: 31.4% squamous, 49.8% adenocarcinoma, 15.3% large cell and undifferentiated and 3.5% other. There was a significant difference in the plasmatic levels of VEGFR2 between c and p (mean± SEM): 6318±152 ng/ml and 8141± 119 ng/ml, respectively (p<0.0001). On the other hand, we found no statistical differences according to sex, histology, or stage. The area under the ROC curve was 0.743 indicating that VEGFR2 is an adequate biomarker for the discrimination between c and p. Dividing the cohort in two subgroups according to VEGFR2 levels: high (>9473,9 ng/ml) and low (≤ 9473,9 ng/ml), we found significant difference in terms of Time to Progression (TTP). Patients with higher levels of VEGFR2 had a median TTP of 204 days whereas in the group with lower expression the median was 164 days, (p= 0.039). Conclusions: In advanced NSCLC, we found higher levels of soluble VEGFR2 in p than in c. There was a correlation between higher expressions of soluble VEGFR2 with better prognosis, in terms of TTP, therefore a more thorough understanding in the role of the plasmatic quantification of this angiogenic receptor in advanced NSCLC p seems to be an important task. No significant financial relationships to disclose.

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