Discussion
a) Key Findings: In this case, the patient’s entire course of treatment covered a comprehensive range of therapeutic measures, with the effects of chemotherapy alone, single PD-1 antibody therapy combined with Endostatin, and dual anti-targeted therapy all being demonstrated. In particular, dual anti-targeted therapy with camrelizumab combined with bevacizumab has already been observed to have better efficacy in 18 months of treatment with no significant adverse effects, providing a new referenceable treatment option for patients with advanced NSCLC with Kras mutation.
b) Strengths and limitations: NSCLC accounts for more than 80 % of lung cancers, the vast majority of which were found to be in advanced inoperable stages. The 2020 guidelines on anti-angiogenesis in advanced NSCLC suggest that platinum-containing chemotherapy combined with anti-angiogenic therapy or immune checkpoint inhibitor immunotherapy is recommended as first-line treatment for patients with advanced non-squamous NSCLC who are negative for driver genes[11]. However, only a small proportion of patients may benefit from treatment with PD-1/PD-L1 antibodies alone, which may be related to the complexity and dynamics of the tumour microenvironment. While previous reports on Endostatin for the treatment of lung adenocarcinoma combined with malignant pleural fluid have mostly been in combination with AP chemotherapy regimens or TKI, this case explored the clinical efficacy of PD-L1 inhibitors in combination with endostatin and dual anti-targeted therapy. In this case, the patient developed more severe malignant pleural fluid after the conventional 5 cycles of AP regimen chemotherapy, so the treatment regimen was adjusted to endostatin and camrelizumab, which was more effective. After more than a year of maintenance treatment with a PD-1 inhibitor in combination with endostatin (during which proton heavy ion therapy was administered to kill solid tumour lesions), the patient’s condition stabilized and he was now treated with the newly recommended and clinically proven dual-target therapy regimen for further treatment. After 19 cycles of dual anti-targeted therapy, serum lung tumour markers were further controlled. However, the efficacy of this immunotherapy regimen was not well documented in terms of imaging reports as the patient had undergone concurrent proton-heavy ion therapy to eliminate the tumour lesions.
c) Explanations of findings: The occurrence, development and prognosis of lung cancer are closely related to the immune function status of the body and the tumour immune micro environment[12-14]. Evidence suggests that angiogenesis may be associated with immunosuppression of the tumour microenvironment, thereby enhancing the immune escape of tumour cells. Anti-PD-1 or anti-PD-L1 therapy may improve the sensitivity and prolong the efficacy of anti-angiogenic therapy, and conversely anti-angiogenic therapy may improve anti-PDL1 therapy by supporting vascular changes that contribute to enhanced infiltration and activity of toxic T cells, as well as the destruction of tumour cells so that when high endothelial cell micro vein formation is present in the tumour, the combination of anti-angiogenic inhibitors and checkpoint inhibitors produces a more long-lasting effect when combined with checkpoint inhibitors.
d) Implications and actions needed: Patients were monitored for possible adverse reactions under this treatment regimen by regular routine blood, blood biochemistry, and urinary routine examinations. The patient’s renal function was not significantly affected, but the transaminase ratio was high and basically maintained in a stable state. The patient’s lipid level was also within the range of concern due to the combination of fatty liver. The patient did not take appropriate lipid-lowering drugs during our treatment, but we cannot exclude the possibility that the patient had related drugs outside the hospital. During the transition treatment (camrelizumab + bevacizumab + endostatin), a significant increase in both triglyceride levels, total cholesterol levels and transaminase ratios were found in this patient, suggesting that the combination of these three drugs may have had some effect on liver function. A combined analysis of efficacy and adverse effect indicators throughout the treatment period revealed that camrelizumab in combination with bevacizumab had significant efficacy and no significant adverse effects. A study of advanced non-small cells found that the presence of KRAS mutations (G12X, codon 13 and Q61H) was associated with better survival in ≥50% of PD-L1 patients treated with immune checkpoint inhibitor monotherapy, while there was no significant survival difference in patients treated with chemoimmunotherapy[15]. Unfortunately, no data on the classification of KRAS mutation types have been reported. This may be one of the reasons for the better treatment outcome for the patient in this case. Whether all patients with non-small cell lung cancer with KRAS p.Q61H can be treated with this regimen and achieve significant efficacy needs to be further confirmed by more clinical studies.