PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: Results from CASPIAN
Luís Paz-AresJonathan W. GoldmanMarina Chiara GarassinoMikhail DvorkinDmytro TrukhinGalina StatsenkoKatsuyuki HottaJun Ho JiMaximilian J. HochmairОлександр ВойткоLibor HavelArtem PoltoratskiyGyörgy LosonczyNiels ReinmuthYashaswi ShresthaNikunj PatelHelen MannHaiyi JiangMustafa ÖzgüroğluYuanbin Chen
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Prophylactic cranial irradiation
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Meeting abstracts As single agents, durvalumab (MEDI4736), a human IgG1 anti-PD-L1 antibody, and tremelimumab, a human IgG2 anti-CTLA-4 antibody, have shown acceptable safety profiles and antitumor activity. Similar to other anti-PD-L1/anti-PD-1 monotherapies, durvalumab has shown greater objective
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Objective To evaluate the enhanced effects of different concentrations of cyclosporin on chemotherapeutic drugs (carboplatin and etoposide) for inhibiting SO-Rb50 cells in vitro. Methods The research were divided into 7 groups: G1 (carboplatin group), G2 (carboplatin+0.5 mg/L CSA group), G3(carboplatin+1.0 mg/L CSA group), G4(etoposide group), G5 (etoposide+0.5 mg/L CSA group), G6 (etoposide+1.0 mg/L CSA group), and G7 (different concentrations of CSA alone). The effects of 9 different concentrations ( 0.004 mg/L to 1.0 mg/L double in-creased) of chemotherapeutic drugs (carboplatin and etoposide) and chemotherapeutic drugs mixed with cyclosporin (0.5 mg/L and 1.0 mg/L) on SO-Rb50 cells in vitro were studied respectively. MTT method was used to observe the growth inhibition of SO-Rb50 cells in each group. By comparing with the inhibitory rate of Rb cells and IC50 in each group and the modality changes of Rb cells with converted microscope, we could evaluate the effect of CSA on the chemotherapeutic drugs on Rb cells. Results When the chemotherapeutic drugs (carboplatin and etoposide) mixed with differ-ent concentrations of CSA in vitro, the inhibitory rates of chemotherapeutic drugs on SO-Rb50 cells were higher than that in the chemotherapeutic drugs alone. The IC50 (mg/L) in G1～G6 were : 0.335 ,0.183,0.130,0.113 ,0.099 ,0.077, respectively . When CSA mixed with chemotherapeu-tic drugs and the concentration of CSA increased, the IC50 in each group decreased gradually. There were statistical significant differences in the inhibitory rates and IC50 among G1,G2,G3 and G4,G5,G6 .The inhibitory rate was not related to CSA concentration in G7 group. Under the coverted micro-scope , the modality changes of Rb cells in group with CSA and chemotherapeutic drugs were marked-ly different from that with chemotherapeutic drugs alone. Conclusions CSA alone has no inhibitory ef-fect on Rb cells alone. Different concentrations of CSA can enhanced the inhibitory effects of chemotherapeutic drugs ( carboplatin and etoposide) on Rb cells in vitro. The higher the concentra-tions of CSA, the more significant the inhibitory effects of carboplatin and etoposide on Rb cells .
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Introduction: Immune checkpoint inhibitors, monoclonal antibodies directed against programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), have broadened treatment options for patients with non-small cell lung cancer (NSCLC). Durvalumab is a selective, high-affinity, human IgG1 monoclonal anti-PD-L1 antibody that blocks interactions of PD-L1 with PD-1 and CD80.Areas covered: We reviewed clinical data supporting the use of durvalumab as a monotherapy and combination therapy for the treatment of locally advanced and advanced NSCLC.Expert commentary: Durvalumab as a monotherapy or combination therapy has shown well-tolerated safety profiles for NSCLC in several trials. Durvalumab monotherapy in advanced NSCLC patients with PD-L1 ≥ 25% as later line (ATLANTIC study) therapy led to clinically meaningful improvements compared to standard of care. Combination therapy comprising durvalumab plus tremelimumab for advanced NSCLC did not show clinical efficacy in three phase III trials. Durvalumab administered after chemoradiotherapy in stage III NSCLC (PACIFIC study) significantly improved progression-free survival and overall survival. This result has led to approval of durvalumab for patients with locally advanced NSCLC as the standard of care. Ongoing trials provide insight into how durvalumab fits into the rapidly evolving therapeutic landscape for locally advanced or advanced NSCLC.
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Small cell lung cancer (SCLC) will account for approximately 20%-25% of the 171,500 estimated new lung cancer cases in 1998. Combination cytotoxic therapies have yielded the best response rates in SCLC patients. Cisplatin in combination with etoposide is used routinely in the treatment of SCLC. Because of cisplatin's nonhematologic toxicities, carboplatin was developed and has far fewer nonhematologic toxicities. Carboplatin in combination with etoposide has been shown to be as effective as, but less toxic than, cisplatin/etoposide. Moreover, carboplatin/etoposide is a viable combination in the treatment of the elderly with SCLC, who can readily tolerate this combination. Concurrent radiation therapy with carboplatin and etoposide in patients with limited SCLC disease can be given safely and effectively. Carboplatin has been combined with several different chemotherapeutic agents, including ifosfamide, and, more recently, paclitaxel in hopes of improving the response rates and overall survival. In order to try to dose intensify carboplatin-based regimens, peripheral blood stem cells have been used to decrease the hematologic toxicities. Further studies are warranted to investigate these therapies as well as newer carboplatin combinations.
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Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.
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