Background: Cisplatin, etoposide and irinotecan are primary drugs in the treatment of small cell lung cancer. We did this retrospective study to investigate whether combined chemotherapy with cisplatin, etoposide, and irinotecan was better than topotecan alone as second-line chemotherapy in patients with sensitive relapsed SCLC. Method: Between 1st Sep, 2014 and 30th Sep, 2017，We collected the patients information in Jilin Province Cancer Hospital. All patients with SCLC responded in first-line treatment and showed radiological evidence of disease relapse or progression at least 90 days after completion of the first-line treatment. 36 patients received combination chemotherapy with cisplatin plus etoposide plus irinotecan and 42 patients received topotecan alone. Combination chemotherapy consisted of five 2-week courses of intravenous cisplatin 25 mg/m 2 on days 1 and 8, intravenous etoposide 60 mg/m 2 on days 1e3, and intravenous irinotecan 90 mg/m 2 on day 8. Topotecan therapy consisted of four courses of intravenous topotecan 1.0 mg/m 2 on days 1e5, every 3 weeks. The primary endpoint was overall survival, which was analysed with a onesided a of 5%, and safety was assessed in all patients who received at least one dose of drugs. Results: The median follow-up for patients was 20.6 months (IQR 17.1e26.9). Overall survival was significantly longer in the combination chemotherapy group (median 16.3 months, 95% CI 13.8e19.1) than in the topotecan group (13.1 months, 10.2e15.4; hazard ratio 0.72, 90% CI 0.58e0.83; p¼0.0097). The most common grade 3/4 adverse events were neutropenia (31 [86.1%] patients in the combination chemotherapy group vs 28 [66.7%] patients in the topotecan group), anaemia (26 [72.2%] vs 10 [23.8%]), and leucopenia (29 [80.6%] vs 21 [50.0%]). Grade 3/4 febrile neutropenia was more common in the combination chemotherapy group than in the topotecan group (10 [27.8%] vs 4[9.5%]), as was grade 3/4 thrombocytopenia (13 [36.1%] vs 11 [26.2%]). One treatment-related death (febrile neutropenia with pulmonary infection) occurred in the combination chemotherapy group and none in the topotecan group. Conclusion: Combination chemotherapy with cisplatin plus etoposide plus irinotecan could be considered as a treatment option in secondline chemotherapy for selected patients with sensitive relapsed SCLC. But the combination chemotherapy group had higher incidence of adverse events than the topotecan group and we should explore appropriate drug dosages in Chinese people.

different receptors, multi-specific antibodies with the capacity to blockade of multiple targets or binding sites are showing improved therapeutic efficacy against cancer. Although "knobs-into-holes" technique is an efficient way to generate bispecific antibody with whole IgG-architecture, the efficacy of different heavy chain hetero-generation and the thermostability remain questionable. How to efficiently generate tetra-specific antibodies with more efficiency and stability is critical for the development of novel antibodies against cancer. Method: By using the structure-based computational design and longtime molecule dynamic simulation (5 ms), we have successfully developed a more efficient technique "Lock-and-key" to produce bispecific antibodies with more efficiency. Based on the parent EGFR antibody cetuximab, PD-L1 antibody atezolizumab, VEGF antibody bevacizumaband CTLA-4 antibody ipilimumab, EGFR tetra-specific antibody with whole IgG structure was designed. Results: With the benefits of multispecific antibody and whole IgG architecture, the EGFR tetra-specific antibody could specifically target EGFR, PD-L1, VEGF and CTLA-4, exhibiting potent anti-tumor efficacy than the combination of Cetuximab, Atezolizumab, Bevacizumab and Ipilimumab against NSCLC. Conclusion: "Lock-and-Key" technique could be a more promising method to produce the multi-specific antibody. More importantly, multi-specific antibody with whole intact IgG structure shows the advantages in cancer treatment. Antagonism of EGFR, PD-L1, VEGF and CTLA-4 through multi-specific antibody could be a promising anti-tumor strategy against NSCLC. Keyword: Multi-specific antibody, nonsmall cell lung cancer, tumor microenvironment

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Background: Cisplatin, etoposide and irinotecan are primary drugs in the treatment of small cell lung cancer. We did this retrospective study to investigate whether combined chemotherapy with cisplatin, etoposide, and irinotecan was better than topotecan alone as second-line chemotherapy in patients with sensitive relapsed SCLC. Method: Between 1st Sep, 2014 and 30th Sep, 2017，We collected the patients information in Jilin Province Cancer Hospital. All patients with SCLC responded in first-line treatment and showed radiological evidence of disease relapse or progression at least 90 days after completion of the first-line treatment. 36 patients received combination chemotherapy with cisplatin plus etoposide plus irinotecan and 42 patients received topotecan alone. Combination chemotherapy consisted of five 2-week courses of intravenous cisplatin 25 mg/m 2 on days 1 and 8, intravenous etoposide 60 mg/m 2 on days 1e3, and intravenous irinotecan 90 mg/m 2 on day 8. Topotecan therapy consisted of four courses of intravenous topotecan 1.0 mg/m 2 on days 1e5, every 3 weeks. The primary endpoint was overall survival, which was analysed with a onesided a of 5%, and safety was assessed in all patients who received at least one dose of drugs. Results: The median follow-up for patients was 20.6 months (IQR 17.1e26.9). Overall survival was significantly longer in the combination chemotherapy group (median 16.3 months, 95% CI 13.8e19.1) than in the topotecan group (13.1 months, 10.2e15.4; hazard ratio 0.72, 90% CI 0.58e0.83; p¼0.0097). The most common grade 3/4 adverse events were neutropenia (31 [86.1%] patients in the combination chemotherapy group vs 28 [66.7%] patients in the topotecan group), anaemia (26 [72.2%] vs 10 [23.8%]), and leucopenia (29 [80.6%] vs 21 [50.0%]). Grade 3/4 febrile neutropenia was more common in the combination chemotherapy group than in the topotecan group (10 [27.8%] vs 4[9.5%]), as was grade 3/4 thrombocytopenia (13 [36.1%] vs 11 [26.2%]). One treatment-related death (febrile neutropenia with pulmonary infection) occurred in the combination chemotherapy group and none in the topotecan group. Conclusion: Combination chemotherapy with cisplatin plus etoposide plus irinotecan could be considered as a treatment option in secondline chemotherapy for selected patients with sensitive relapsed SCLC. But the combination chemotherapy group had higher incidence of adverse events than the topotecan group and we should explore appropriate drug dosages in Chinese people.

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