Tolerability, safety, and preliminary antitumor activity of fuzuloparib in combination with SHR-1316 in patients with relapsed small cell lung cancer: a multicenter, open-label, two-stage, phase Ib trial.

Background: Second-line treatment options for small cell lung cancer (SCLC) are limited. Preclinical research shows that inhibition of poly (ADP-ribose) polymerase (PARP) could upregulate programmed death-ligand 1 (PD-L1), and thus render cancer cells more sensitive to immune checkpoint inhibitors. This study investigated the tolerability, safety, and preliminary antitumor activity of fuzuloparib (a PARP inhibitor) plus SHR-1316 (a PD-L1 inhibitor) for relapsed SCLC. Methods: Patients with SCLC who failed previous first-line platinum-based therapy were enrolled in this two-stage phase Ib trial. In stage 1, 2 dose levels were designed: fuzuloparib 100 mg or 150 mg twice daily plus SHR-1316 600 mg every 2 weeks, with 6 patients in each dose level. Based on the tolerability during the first 28-day cycle and the preliminary antitumor activity in stage 1, a recommended phase II dose (RP2D) was determined and introduced in the stage 2 expansion phase. The primary endpoints were safety and RP2D in stage 1 and objective response rate (ORR) in stage 2. Results: A total of 23 patients were enrolled, with 16 receiving fuzuloparib 100 mg plus SHR-1316 and 7 receiving fuzuloparib 150 mg plus SHR-1316. At data cutoff on April 23, 2021, the median follow-up duration was 6.4 months (IQR, 3.0-9.7 months). All patients discontinued study treatment. One patient receiving fuzuloparib 150 mg plus SHR-1316 had clinically significant toxicities, and fuzuloparib 100 mg plus SHR-1316 was considered as the RP2D. In the RP2D cohort, the confirmed ORR was 6.3% (95% CI: 0.2-30.2%), and the disease control rate was 37.5% (95% CI: 15.2-64.6%). The median progression-free survival was 1.4 months (95% CI: 1.3-2.8 months), and the median overall survival was 5.6 months (95% CI: 3.0-16.7 months). Grade ≥3 treatment-related adverse events (TRAE) occurred in 8 patients (34.8%). No treatment-related death occurred, and no patients discontinued treatment due to TRAEs. Conclusions: Fuzuloparib combined with SHR-1316 failed to improve the outcomes in unselected patients with relapsed SCLC. Future studies with biomarker analysis are warranted to select patients most likely to benefit from this combination treatment. Fuzuloparib 100 and 150 mg plus SHR-1316 were both tolerable with no new signals observed.

Sex Differences in the Incidence and Clearance of Anogenital Human Papillomavirus Infection in Liuzhou, China: An Observational Cohort Study.

BACKGROUND: Human papillomavirus (HPV) causes anogenital warts and cancers in men and women. However, little is known about sex differences regarding the natural history of anogenital HPV infection. METHODS: Starting in May 2014, an observational cohort study including 2309 men and 2378 women aged 18-55 years was conducted in Liuzhou, China. Samples from anogenital sites were tested for HPV genotypes by multicolor real-time polymerase chain reaction and melting curve analysis biannually for ~1 year. RESULTS: The incidence of oncogenic HPV infection was similar in men and women (10.3 and 11.5/1000 person-months; P = .275), whereas the incidence of HPV-6/11 infection was higher in men than in women (2.0 vs 1.1; P = .018). The incidence of both oncogenic HPV and HPV-6/11 infections was significantly higher in women in the 18- to 25-year age group than in the older age groups (P = .006 and .011, respectively), whereas it did not vary by age among men (P = .552 and .425, respectively). Additionally, men were more likely than women to clear oncogenic infections (101.5 vs 58.6/1000 person-months; P < .001), but no significant difference was found in the clearance of HPV-6/11 by sex (111.7 vs 84.8; P = .266). The median time to clearance of oncogenic type and type 6/11 infections was not age dependent for either sex (all P > .05). CONCLUSIONS: The natural history of oncogenic and nononcogenic HPV infection differs by sex, which implies that sex-specific vaccination strategies should be considered for oncogenic and nononcogenic HPV. CLINICAL TRIALS REGISTRATION: NCT02188004.

Incidence of anogenital warts in Liuzhou, south China: a comparison of data from a prospective study and from the national surveillance system.

To determine the incidence of anogenital warts (AGWs) in the Chinese general population, we compared the data from a prospective study and from the National Notifiable Disease Report System (NNDRS). A cohort study including 2378 women and 2309 men aged 18-55 years old enrolled from Liuzhou, China, was conducted with three scheduled visits at 6-month intervals from May 2014 to March 2016. And, a questionnaire survey was performed to collect the diagnosis history of AGWs at the enrollment visit. The data on reported AGW cases of Liuzhou in the NNDRS from 2006 to 2015 were also analyzed. Overall, the incidence rates of AGWs in the prospective study, in the self-reported diagnosis during past 12 months and in the NNDRS were 1.26 per 1000 person-years (95% confidence interval (CI): 0.16-2.37), 2.35 (95% CI: 1.17-4.20) and 0.183 (95% CI: 0.178-0.187), respectively. Human papillomavirus 6 or 11 were found in all the AGW biopsy samples (10/10). The onset time of AGWs in women was earlier, and the cumulative risk increased more quickly at a young age along with each subsequent younger birth cohort (P<0.0001), whereas slight differences were observed in the different male birth cohorts (P=0.0785). The sexual behavior of individuals and their sexual partners had a strong relationship with self-reported AGWs. Our study indicates that the incidence of AGWs in China is as high as that in developed countries, and the data based on the national surveillance system seriously underestimate the real disease burden of AGWs.