Efficacy and safety of anti-PD-1 antibody plus regorafenib in refractory microsatellite stable metastatic colorectal cancer: a retrospective single-arm cohort study.

Background: Managements for refractory proficient mismatch repair (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) were still challenging and controversial. Our study sought to investigate the efficacy and safety of anti-programmed cell death protein 1 (anti-PD-1) antibodies plus regorafenib in refractory pMMR/MSS mCRC. Methods: We retrospectively analyzed the efficacy and safety of 103 pMMR/MSS mCRC patients treated with at least one dose of anti-PD-1 antibodies plus regorafenib (80 mg once daily for 21 days on/7 days off 28 days as a cycle) between July 2019 and June 2021 at the Hunan Cancer Hospital. All patients had previously received at least second-line treatment. The patients were evaluated by computed tomography every 2 or 3 treatment cycles until progression or being lost to follow-up. The primary end point was overall survival (OS). Results: The median follow-up period was 5.30 (range, 0.50-22.50) months. The median OS (mOS) and medical progression-free survival (mPFS) were 8.40 and 2.50 months for the entire cohort, respectively. The mOS and mPFS were 16.07 and 3.10 months in patients who received >1 cycle of anti-PD-1 antibodies and regorafenib (n=55), which were significantly longer than 4.37 and 1.11 months in those received only 1 cycle (n=48) (both P<0.001, respectively). The Cox multivariate regression analysis demonstrated that the number of cycles of regorafenib plus PD-1 and previously undergone surgery were independent risk factors for OS, whereas Sintilimab was confirmed to have a significant better PFS compared to other anti-PD-1 antibodies. Of the 55 patients who were evaluated, 7 were diagnosed with a partial response (PR) and another 16 were diagnosed with stable disease (SD), but no patient showed a complete response (CR). Thus, the objective response rate (ORR) was 12.7% and the disease control rate was 41.8%. Treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 13 (12.6%) patients. Conclusions: The combination of regorafenib plus anti-PD-1 antibodies has a manageable safety profile and may improve prognosis for pMMR/MSS mCRC patients, especially those who received >1 cycle. Compared to the other anti-PD-1 antibodies, sintilimab may be more efficacious; however, further prospective studies need to be conducted to confirm our findings.

Quantum simulation of tunable and ultrastrong mixed-optomechanics.

We propose a reliable scheme to simulate tunable and ultrastrong mixed (first-order and quadratic optomechanical couplings coexisting) optomechanical interactions in a coupled two-mode bosonic system, in which the two modes are coupled by a cross-Kerr interaction and one of the two modes is driven through both the single- and two-excitation processes. We show that the mixed-optomechanical interactions can enter the single-photon strong-coupling and even ultrastrong-coupling regimes. The strengths of both the first-order and quadratic optomechanical couplings can be controlled on demand, and hence first-order, quadratic, and mixed optomechanical models can be realized. In particular, the thermal noise of the driven mode can be suppressed totally by introducing a proper squeezed vacuum bath. We also study how to generate the superposition of coherent squeezed state and vacuum state based on the simulated interactions. The quantum coherence effect in the generated states is characterized by calculating the Wigner function in both the closed- and open-system cases. This work will pave the way to the observation and application of ultrastrong optomechanical effects in quantum simulators.

Quantum entanglement maintained by virtual excitations in an ultrastrongly-coupled-oscillator system.

We study the effect of quantum entanglement maintained by virtual excitations in an ultrastrongly-coupled harmonic-oscillator system. Here, the quantum entanglement is caused by the counterrotating interaction terms and hence it is maintained by the virtual excitations. We obtain the analytical expression for the ground state of the system and analyze the relationship between the average excitation numbers and the ground-state entanglement. We also study the entanglement dynamics between the two oscillators in both the closed- and open-system cases. In the latter case, the quantum master equation is microscopically derived in the normal-mode representation of the coupled-oscillator system. This work will open a route to the study of quantum information processing and quantum physics based on virtual excitations.