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NGR-hTNF and Doxorubicin as Second-Line Treatment of Patients with Small Cell Lung Cancer.

ABSTRACT: LESSONS LEARNED:NGR-hTNF was safely combined with doxorubicin, showing a promising antitumor activity in unselected patients with relapsed small cell lung cancer.Similar antitumor activity was observed in platinum-sensitive and platinum-resistant patient cohorts. BACKGROUND:Relapsed small cell lung cancer (SCLC) patients have limited treatment options and poor outcomes. NGR-hTNF is a vascular-targeting agent, which increases intratumoral chemotherapy penetration and T-lymphocyte infiltration. METHODS:Twenty-eight patients relapsing after at least one platinum-based regimen with a treatment-free interval shorter (n?=?16; platinum-resistant) or longer (n?=?12; platinum-sensitive) than 3 months received NGR-hTNF 0.8 ?g/m2 plus doxorubicin 75 mg/m2 every 3 weeks. The primary endpoint of this single-arm phase II trial was progression-free survival (PFS), and safety, response rate, and survival were secondary endpoints. RESULTS:The most common grade 3-4 toxicities were neutropenia (53%) and anemia (21%). Median PFS was 3.2 months for all patients, 2.7 months for platinum-resistant patients, and 4.1 months for platinum-sensitive patients. Seven patients had partial responses (25%), including four (25%) with platinum-resistant and three (25%) with platinum-sensitive relapse. Mean changes from baseline in tumor burden (after two, four, and six cycles) did not differ between platinum-resistant (-9%, -29%, and -32%) and platinum-sensitive (-11%, -20%, and -43%) cohorts. Overall survival was associated only with baseline lymphocyte counts, with median survival times of 13.1 and 5.2 months for lymphocyte counts above or below the median, respectively. CONCLUSION:NGR-hTNF plus doxorubicin showed manageable toxicity and promising activity in patients with relapsed SCLC.

SUBMITTER: Gregorc V

PROVIDER: S-EPMC6263121 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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NGR-hTNF and Doxorubicin as Second-Line Treatment of Patients with Small Cell Lung Cancer.

Gregorc Vanesa V Cavina Raffaele R Novello Sivia S Grossi Francesco F Lazzari Chiara C Capelletto Enrica E Genova Carlo C Salini Giulia G Lambiase Antonio A Santoro Armando A

The oncologist 20180803 10

<h4>Lessons learned</h4>NGR-hTNF was safely combined with doxorubicin, showing a promising antitumor activity in unselected patients with relapsed small cell lung cancer.Similar antitumor activity was observed in platinum-sensitive and platinum-resistant patient cohorts.<h4>Background</h4>Relapsed small cell lung cancer (SCLC) patients have limited treatment options and poor outcomes. NGR-hTNF is a vascular-targeting agent, which increases intratumoral chemotherapy penetration and T-lymphocyte i ...[more]

PMID: 30076277

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Project description:Dacomitinib is a second-generation, irreversible, covalent pan-HER tyrosine-kinase inhibitor (TKI). It showed potent EGFR signaling inhibition in experimental models, including first-generation TKI-resistant non-small cell lung cancer (NSCLC) cell lines. This preclinical efficacy did not translate into clinically meaningful treatment benefits for advanced, pretreated, molecularly unselected NSCLC patients enrolled in two parallel phase III trials. Dacomitinib and erlotinib showed overlapping efficacy data in chemotherapy-pretreated EGFR wild-type (WT) patients in the ARCHER 1009 trial. Similarly, it failed to demonstrate any survival benefits as compared to placebo in EGFR WT subsets progressing on chemotherapy and at least one previous first-generation TKI (erlotinib or gefitinib) in the BR.26 trial. In the case of EGFR-mutant NSCLCs, a pooled analysis of the ARCHER 1009 and ARCHER 1028 trials comparing the efficacy of dacomitinib vs. erlotinib in chemotherapy-pretreated, EGFR TKI-naïve patients showed a trend to a longer progression-free survival (PFS) and overall survival in favor of dacomitinib that did not reach statistical significance, with a higher rate of treatment related adverse events (mainly skin rash, paronychia, and gastrointestinal toxicities). On the other hand, the clinical activity in patients with EGFR-mutant NSCLCs with acquired TKI resistance that were included in phase II/III trials was equally poor (response rate <10%; PFS 3-4 months). Therefore, with the results of the ARCHER 1050 trial (NCT01774721) still pending, the current clinical development of dacomitinib is largely focused on EGFR-mutant, TKI-naïve patients. Here, we review the most relevant clinical data of dacomitinib in advanced NSCLC. We discuss the potential role of dacomitinib in pretreated EGFR WT and EGFR-mutant (TKI-naïve and TKI-resistant) patients. Finally, we briefly comment the available clinical data of dacomitinib in HER2-mutant NSCLC patients.

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NGR-hTNF and Doxorubicin as Second-Line Treatment of Patients with Small Cell Lung Cancer.

Publications

NGR-hTNF and Doxorubicin as Second-Line Treatment of Patients with Small Cell Lung Cancer.

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