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Introduction: Inhibitors of programmed cell death 1 (PD1) and its ligand (PDL1) have exhibited favorable long-term survival in many types of advanced-stage cancer and current approvals have to date been granted in certain tumour types irrespective of PD-L1 status.Methods: We extracted the following information: study sample size, trial period, cancer types, intervention of treatment, type of PD-L1 antibody, immunohistochemistry (IHC) scoring method, number and percentage of PD-L1 < 1% population, and median follow- up time. PD-L1 expression was defined as percentage of number of PD-L1-stained tumor cells (TPS), area of tumor infiltrated by PD-L1-stained immune cells (IPS), number of PD-L1-stained cells (tumor cells, lymphocytes and macrophages; CPS). Different trials used distinct method to define low PD-L1 expression. The risk of bias of the included trials was assessed by using the Cochrane risk of bias tool for RCTs.Results: Here, a total of 34 trials were included to extract individual patient data (IPD) to evaluate the survival benefit of first line PD1/PDL1 inhibitors vs. standard-of-care (SOC) in patients with PDL1 < 1%. In term of anti-PD-1/PD-L1 monotherapy, OS (HR = 0.90, 0.81−1.01) and PFS (HR = 1.11, 0.97−1.27) between PD-1/PD-L1 inhibitor group and SOC group were comparable. In term of anti-PD-1/PD-L1 combination therapy, PD-1/PD-L1 inhibitor group exhibited longer OS (median 19.5 months vs. 16.3 months; HR = 0.83, 0.79−0.88, p < 0.001) and PFS than those of SOC group (median 8.11 months vs. 6.96 months; HR = 0.82, 0.77−0.87, p < 0.001).Subgroup analysis showed that survival benefit was mainly observed in non-small cell lung cancer (NSCLC) (HROS = 0.74; HRPFS = 0.69; p < 0.001), small-cell lung cancer (SCLC) (HROS = 0.58, p < 0.001; HRPFS = 0.55, p = 0.030), esophageal squamous cell carcinoma (ESCC) (HROS = 0.62, p = 0.005; HRPFS = 0.79, p < 0.001), melanoma (HROS = 0.53, p < 0.001) and nasopharyngeal carcinoma (NPC) (HRPFS = 0.35, p = 0.013).Conclusion: Anti-PD-1/PD-L1 combinational therapy rather than monotherapy exhibit survival benefit in the low PD-L1 population in the first-line setting, and the survival benefit was mainly observed in specific tumor types.

An ultra-low quiescent current output-capacitor-less low dropout (OCL-LDO) regulator for power-sensitive applications is proposed in this paper. To improve the gain of the OCL-LDO feedback loop, the error amplifier employs a combination of a cross-coupled input stage for boosting the equivalent input transconductance and a negative resistance technique to improve the gain. Meanwhile, in order to address the issue of transient response of the ultra-low quiescent current OCL-LDO, a sub-threshold slew-rate enhancement circuit is proposed in this paper, which consists of a transient signal input stage and a slew-rate current increase branch. The proposed OCL-LDO is fabricated in a 0.18 μm CMOS process with an effective area of 0.049 mm2. According to the measurement results, the proposed OCL-LDO has a maximum load current of 100 mA and a minimum quiescent current of 640 nA at an input voltage of 1.2 V and an output voltage of 1 V. The overshoot and undershoot voltages are 197 mV and 201 mV, respectively, and the PSR of the OCL-LDO is −72.4 dB at 1 kHz when the load current is 100 μA. In addition, the OCL-LDO has a load regulation of 7.6 μV/mA and a line regulation of 0.87 mV/V.