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.