Whole-course management of real-world EGFR-mutant lung adenocarcinoma targeting combined with anti-angiogenic therapy mode China Thoracic Oncology Conference

The multidisciplinary diagnosis and treatment model plays an important role in the comprehensive treatment of cancer patients.
By combining medical oncology, surgical oncology, radiotherapy, imaging, pathology and other related departments to comprehensively evaluate, analyze and discuss the patient's condition, so as to jointly formulate scientific, A reasonable and standardized treatment plan can effectively improve the survival rate of cancer patients and improve their quality of life
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Since 2003, the Guangdong Lung Cancer Research Institute of Guangdong Provincial People's Hospital, under the leadership of Professor Wu Yilong, has carried out multidisciplinary case discussions on lung cancer every Wednesday afternoon.
Over the past two decades, it has provided thousands of patients with better diagnosis and treatment decisions.
It has also cultivated the ability of multidisciplinary thinking and collaboration among many oncologists
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On this basis, in March 2021, the Lung Oncology Branch of the Guangdong Medical Association and the Guangdong Clinical Trials Association/China Thoracic Oncology Research Assistance Group (GACT/CTONG) will organize various specialties in the clinical field of lung cancer in Guangdong Province.
The experts from the hospital carried out the monthly "Guangdong General Consultation" project for difficult cases of lung cancer.
During the 10 consultations, experts in various fields showed their strengths, arguing, brainstorming, and applying the evidence of evidence-based medicine to specific personalities.
In the case of chemical treatment, it fully embodies that "medicine is an art based on science"
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Through online live broadcast and major media reports, the project has a wide influence in the domestic lung cancer clinical medical community, and has played a good role in promoting the standardized multidisciplinary diagnosis and treatment of lung cancer
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Encouraged by the successful holding of the "Guangdong Conference", in order to gather the wisdom of experts from a wider range and promote the multidisciplinary expert diagnosis and treatment model for lung cancer more widely, the Lung Oncology Branch of the Guangdong Medical Association and the Guangdong Clinical Trials Association/China The Thoracic Oncology Research Assistance Group (GACT/CTONG) has jointly launched the "China Thoracic Oncology Conference" event in February 2022, which is currently the first nationwide expert on-site consultation event for lung cancer and other thoracic tumors
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We will invite experts from all over the country in the field of thoracic tumor treatment to form a consultation decision-making team, and conduct multidisciplinary consultations on representative and difficult cases of lung cancer on a monthly basis.
Contribute to the tough task of diagnosis and treatment of lung cancer in China
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The first China Thoracic Oncology Conference was held on February 25
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Cases of this conference 1.
Case introduction ▶Summary of medical history 64 years old, male, PS1 points
.

He visited our hospital on 2019-02-11 due to "repeated dry cough for more than 3 months"
.

The patient developed paroxysmal dry cough without obvious incentive more than 3 months ago.
On 2019-1-29, chest CT enhancement in a foreign hospital showed: a mass (3.
5*2.
2cm) in the apical segment of the upper lobe of the right lung, considering peripheral lung cancer, bilateral hilum, There were multiple enlarged lymph nodes in the mediastinum, and multiple metastases in both lungs and bilateral pleura
.

Past history: Hepatitis B "small three yang" history of more than 10 years, no antiviral treatment; personal history: smoking 15 packs/year, has been abstinent for 1 year; family history: his father's history of bowel cancer
.

▶Pathology On February 19, 2019, a biopsy of the left supraclavicular lymph node was performed in our hospital.
Pathology: metastatic adenocarcinoma
.

Immunohistochemistry: tumor cells CK7 (+++), TTF1 (+++), immunophenotype supports lung origin
.

PDL1 (22C3): TPS 10%+
.

Figure 1.
Left supraclavicular lymph node showing adenocarcinoma invasion.
Diagnosis: right upper lung adenocarcinoma cT4(IpsiNod)N3M1a (contralateral lung, pleura) stage IVA
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Next-generation sequencing (NGS) results were included in the 425-gene panel NGS of the TRUMP research line: EGFR 19del mutation p.
L747_A755delinsPRS and multiple coexisting gene variants
.

Table 1.
NGS test results ▶ After first-line erlotinib + bevacizumab (A+T), the efficacy evaluation was partially effective (partial response, PR), 3° oral ulcers, rash; 1° ALT, AST Elevated, to entecavir, liver protection treatment
.

Due to toxic and side effects, erlotinib was changed to gefitinib in combination, PFS1=5.
8 months
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Gefitinib + bevacizumab, maintained PR, 2° epistaxis, 1° ALT, AST increased, bevacizumab dose was reduced to 300 mg, PFS2=17.
7 months
.

▶Image 2.
From left to right: 2019-1 (baseline), 2019-6 (erlotinib + bevacizumab), 2020-10 (gefitinib + bevacizumab) 2021-02-03 The enhanced MR of the head indicated multiple brain parenchymal metastases, the lung maintained PR, and the disease progression (PD) was evaluated, and local progression was considered
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Figure 3.
Cranial MRI image re-biopsy to clarify the mechanism of drug resistance ▪ In February 2021 and March 2021, two lumbar punctures were performed, and the cerebrospinal fluid NGS showed no mutation, and the cerebrospinal fluid was tested by TCT1 No cancer cells were seen once, and suspicious cancer cells were seen once
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No mutation was found in the peripheral blood NGS submitted for examination
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To sum up, cancer cells were seen in cerebrospinal fluid, and meningeal metastasis was considered in combination with clinical practice
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Figure 4.
Suspected cancer cells in cerebrospinal fluid ▪ Considering that the patient had asymptomatic brain and meningeal metastases, gefitinib + bevacizumab therapy was continued
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▶After continuous gefitinib + bevacizumab therapy, 3° proteinuria, PFS3=11.
7 months, re-evaluation of PD in 2022-January, comprehensive progress (enlarged primary tumor, increased brain metastases, new sternum and C7 metastases) ABC new sternal metastases Figure 5.
Imaging results of multi-organ metastases: A: lung CT; B: brain MR; C: sternal CT re-biopsy to clarify the drug resistance mechanism 2022-2-23 Blood 10 genes NGS: EGFR 19del mutation (AF 0.
27%), EGFR T790M mutation (AF 0.
41%)
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Puncture pathology of right upper lung tumor: lung invasive adenocarcinoma, PDL1: TPS 1%+, MET FISH(-); 2022-2-24 tissue 520 gene panel NGS: EGFR DEL19 mutation (AF 24.
41%), EGFR T790M mutation (AF 15.
99%), EGFR exon 18 G724S mutation (AF 5.
79%), and multiple co-mutations
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Table 2.
NGD results of lung cancer puncture tissue △ The patient and his family refused to undergo cerebrospinal fluid examination because there was no clear positive result of NGS in the past two consecutive lumbar punctures
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History Summary A 64-year-old male, smoker, with PS1 score
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Lung adenocarcinoma stage IVA was diagnosed in 2019, with EGFR 19del mutation combined with multiple coexisting variants
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First-line A+T mode: received erlotinib, gefitinib + bevacizumab successively, total PFS=35.
2 months
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The overall tolerability was good, and the EGFR-TKI and bevacizumab were reduced due to 2-3° adverse reactions during the period
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Intracranial asymptomatic local progression re-biopsy showed no clear drug resistance mechanism, and continued medication has clinical benefits
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At present, comprehensive progress has been made, and EGFR T790M mutation, EGFR G724S and other coexisting mutations have been detected in drug-resistant samples
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▶Treatment timeline 2.
Supplementary medical history Xie Shufei (Deputy Chief Physician of the Department of Imaging, Guangdong Provincial People's Hospital): The patient's baseline imaging showed no clear bone metastases, and the current imaging shows clear bone metastases, showing osteolytic destruction.
Prompt progress; intracranial lesions gradually increased, slightly increased, slow progress
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Zhang Yongchang (Deputy Chief Physician, Department of Medical Oncology, Hunan Cancer Hospital): Is 3° proteinuria a 24-hour urine protein quantification? Zhang Yichen (Reporter of Guangdong Lung Cancer Research Institute): No, the patient's 3° proteinuria was albumin +++ or ++++ in the urine routine
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Zhang Yongchang: Clinically, when the albumin +++ in the urine routine of patients, if the 24-hour urine protein is detected, 50% may appear <1g
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This may need to be improved
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Has the evaluation of cardiac EF and ejection fraction been improved by echocardiography during the use of bevacizumab? Zhang Yichen: The patient's baseline cardiac EF and ejection fraction assessments were normal
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Zhang Yongchang: At present, experts recommend that patients using bevacizumab should undergo a cardiac ultrasound examination every two months to evaluate the toxicity of bevacizumab in congestive heart failure
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Dong Zhongyi (attending physician of the Department of Radiotherapy, Southern Hospital of Southern Medical University): The patient is currently progressing in an all-round way, and the number of intracranial lesions is increasing.
Does the patient have corresponding intracranial symptoms now? Zhang Yichen: At present, the patient has no symptoms of intracranial metastasis, no nausea and vomiting, no limb weakness, and no dizziness, headache and other discomforts
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Huang Zhenhua (Deputy Chief Physician, Department of Oncology, Nanfang Hospital, Southern Medical University): The patient has completed two lumbar puncture examinations.
Is the cerebrospinal fluid pressure high? Zhang Yichen: Not high
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Kang Jin (Reporter of Case 1 of Guangdong Lung Cancer Research Institute): May I ask Director Yan from the Department of Pathology, can a patient with suspected cancer cells in the cerebrospinal fluid be able to identify meningeal metastasis? Yan Lixu (Deputy Chief Physician, Department of Pathology, Guangdong Provincial People's Hospital): These five cells are definite tumor cells.
The first feature is that the cells are significantly enlarged under the microscope; the second feature is that the nucleoli of tumor cells are very prominent.
, the red arrow in the figure below shows the nucleolus of the cell, and the middle blue dye is the nucleus; the third feature is that the nuclear membrane is very irregular, so these three points highly support it as a cancer cell
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Wu Yilong (Professor of Oncology, Guangdong Provincial People's Hospital): Corrected a place in the medical history report.
The patient replaced Tarceva with Iressa due to toxicity intolerance rather than progression.
This situation cannot be counted as PFS1
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Case summary of the patient: The patient was treated in A+T mode, with a total PFS of 35.
2 months, and now had toxic side effects, disease progression, and meningeal metastasis.
Drug-resistant samples were found to have EGFR T790M mutation, EGFR G724S, and other coexisting mutations.
How should it be handled? 3.
Question discussion⌛ Question 1: Should the third-generation EGFR-TKI be changed immediately? A.
Yes B.
No C.
Unsure of the voting result: Lin Jie (Chief Physician of the Radiotherapy Department of the Second Affiliated Hospital of Kunming Medical University): Personally choose to change the third-generation EGFR-TKI immediately
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Third-generation EGFR TKIs are firstly able to penetrate the blood-brain barrier and secondly, for EGFR 19del, it is preferred
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Wu Yilong: Everyone agrees.
On the basis of this question, will the patient's EGFR exon 18 G724S mutation interfere with the doctor's choice of diagnosis and treatment? Zhang Yongchang: EGFR 19 deletion can be divided into two types, EGFR 19 deletion and EGFR 19 deletion-insertion.
Our previous study published in the European Journal of Cancer suggested that more than 30 patients with EGFR 19 deletion-insertion received osimertinib Treatment, mPFS=5m, OS=10m, which may remind us that when making treatment decisions for replacement regimens, we need to consider the patient’s deletion type and accompanying mutation type.
Although there is currently no evidence-based medical evidence to guide clinicians What decisions should be made, but We can consider better options
.

Personally choose a double dose of osimertinib or fumetinib.
The first point is that our previous studies suggest that EGFR19 deletion-insertion patients are not effective with osimertinib1, and our previous work suggests that the dose of the drug needs to be increased Steps; The second point is that patients currently have brain metastases.
Osimertinib and fumetinib are different in the human tumor xenograft (PDX) established by our research team, but it is still unclear what the specific mechanism is
.

Huang Zhenhua: Personally, I first consider the third-generation TKI, and choose to use the standard dose of 80 mg.
The patient progresses after the treatment of the current generation of TKI.
In previous clinical studies, the double dose is considered to be patients who do not have T790M mutation after TKI resistance, or have meningeal metastases
.

Director Yan of the Pathology Department analyzed and clarified the patients with meningeal metastasis in detail.
For patients with meningeal metastasis, the dose of 80 mg is effective at the beginning, and the double dose can be considered when the follow-up effect is not good
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Wu Yilong: This patient has brain metastases.
Are you considering radiotherapy? Dong Zhongyi: A study in Nature Communication in 2018 mentioned that the G724S mutation in EGFR exon 18 is a mutation that occurs after the use of osimertinib for the T790M mutation
.

Personally, does this mutation have an impact on the efficacy of osimertinib for the current use of osimertinib as the original mutation rather than the mutation after drug resistance? Some case reports suggest that afatinib can be considered for G724S mutation, or even osimertinib combined with afatinib on the basis of drug-resistant mutations.
There is currently no higher-level evidence-based medical evidence
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Therefore, I personally think that osimertinib should be used immediately.
If osimertinib is effective and the patient does not have any intracranial symptoms, the radiotherapy can be postponed.
The BRAIN study suggests that the delay of radiotherapy will affect the patient's cognitive function and so on.
good protection
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If osimertinib 80 mg is ineffective, a double dose may be considered, or if symptoms related to intracranial metastases appear, radiation therapy may be considered
.

This may depend on whether the efficacy of osimertinib is affected by co-mutation and G724S mutation
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Pan Yi (Chief Physician, Department of Radiotherapy, Guangdong Provincial People's Hospital): I disagree with the current radiotherapy
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Stage IV patients progressed comprehensively after systemic treatment.
First, the patient is currently asymptomatic
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Second, intracranial lesions are multiple, diffuse brain parenchyma lesions, and there are meningeal metastases.
Local only palliative radiotherapy is mainly for whole brain palliative radiotherapy to relieve symptoms
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Third, at present, NGS suggests that T790M mutation, the third-generation TKI is effective for brain metastases, and there are targeted drugs that can be used, so the drug is used first and then whether radiotherapy is observed
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Wu Yilong: During the discussion just now, there were two very interesting questions.
First, do EGFR exon 19 mutations need to be subdivided into subtypes? Second, how should we treat new, very rare subtype mutations? What experience do you have? Wu Fang (Deputy Chief Physician, Department of Medical Oncology, Second Xiangya Hospital, Central South University): Just now Dr.
Dong mentioned that the G724S mutation in EGFR exon 18 appeared after denovo or drug resistance? Recently, we published a case report in the European Journal of Oncology.
This case is a patient with denovo ALK fusion G1202R mutation, and the ALK inhibitor treatment is very effective
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This suggests that rare mutations may also be considered TKI inhibitors
.

The current guidelines support that osimertinib is the first choice for T790M mutation.
I will choose the 80mg dose and then adjust it according to the subsequent efficacy
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Zhou Qing (Chief Physician of the Third Department of Pulmonary, Guangdong Provincial People's Hospital): With the popularization of large-panel NGS, clinicians have more and more understanding and consideration of polygenes, and more and more accompanying genes have been discovered.
It is uncertain how much impact the efficacy of third-generation TKI monotherapy will have
.

Professor Wang Jie's BENEFIT study divides patients into three categories, and divides the nature of accompanying genes into different levels of interference.
The research suggests that the interference of not very strong driver genes may be relatively small
.

The patient A+T benefited for a long time, the tumor growth was relatively slow, and he was currently asymptomatic.
Therefore, if the influence of these accompanying genes is considered, other means should be combined on a single-drug basis, such as double dose or combined chemotherapy or combined anti-vascular, or There is no standard answer as to whether to local treatment or third-generation TKI monotherapy
.

Personally support the evaluation of the efficacy of single-agent osimertinib first, and use the facts to prove whether the influence of these accompanying genes is worth changing the decision of single-agent standard treatment
.

⌛ Question 2: If you switch to a third-generation TKI, should you continue to combine bevacizumab? A.
Yes B.
No C.
Uncertain about the voting result Zhang Yongchang: Personally consider continuing to combine bevacizumab, there are three main points.
First, patients benefit from A+T treatment for a very long time.
I personally think that this should come from two categories.
The synergy of drugs
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Second, the BENEFIT study just mentioned by Director Zhou divides concomitant mutations into three types, which is the current mainstream classification principle for distinguishing concomitant mutations
.

A study published by our team in BMC Medicine suggests3 that the A+T mode of treatment can reverse the negative regulatory effect of this accompanying mutation to a certain extent
.

Third, JAMA oncology has already mentioned 4 that there is no benefit of osimertinib combined with bevacizumab, but individuals choose to continue bevacizumab because the patient can tolerate the toxicity of bevacizumab A retrospective study published in the European Journal of Cancer suggested that patients with brain metastases who received TKI or TKI combined with bevacizumab could improve the vascular microenvironment and finally observed an OS benefit 5
.

Therefore, based on these three considerations, I personally recommend that patients maintain bevacizumab combined with 80mg osimertinib
.

Zhou Chengzhi (Chief Physician, Department of Oncology, The First Affiliated Hospital of Guangzhou Medical University): Combining bevacizumab is not recommended
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The first point is that there is no evidence-based medical evidence to continue to use bevacizumab after the progression of A+T combination therapy
.

The second point is that the patient has been using A+T treatment for a very long time and has poor tolerance.
The dose has been reduced to 300mg, starting from the whole process of management to avoid serious renal damage
.

Susan (Deputy Chief Physician, Department of Medical Oncology, Guangzhou Chest Hospital): I personally support the suspension of bevacizumab.
First, the patient has been using bevacizumab for nearly three years, and the tolerance has declined in all aspects.
Second, the intracranial lesions are stable, and there is no obvious intracranial edema and high pressure.
The third-generation TKI plays a certain role in intracranial lesions.
Third, bevacizumab is currently not used in TKI cross-line therapy.
Supported by medical evidence
.

Huang Zhenhua: I also consider osimertinib 80mg monotherapy.
First, there is currently no evidence-based medical evidence to support osimertinib combined with bevacizumab.
Last year, a clinical study from ESMO from Europe suggested that PFS does not benefit
.

Second, the adverse reaction of bevacizumab, the patient still developed 3° proteinuria even after the dose was reduced to 300 mg
.

Third, from an ethical point of view, when it is necessary to determine whether a treatment plan is feasible, clinicians must be clear about the benefits and supported by evidence-based medical evidence; when there is no better choice, no other choice or after-line treatment, clinicians may Options that are likely to benefit will be selected
.

Now we have made it clear that third-generation osimertinib will definitely benefit
.

Wu Yilong: Three A+T clinical trials from China, Japan and Europe suggest that A+T is a good treatment model
.

In clinical practice, the efficacy of bevacizumab in patients is acceptable and often easy to accept
.

After the emergence of the third-generation EGFR TKI, everyone continued the idea of ​​the first-generation TKI and conducted clinical trials by combining the third-generation TKI with anti-vascular or combined with chemotherapy
.

A major discovery in 2021, the third-generation TKI combined with bevacizumab did not bring benefits to patients, but increased side effects
.

Relevant studies have been published in JAMA oncology4, and another European ETOP 10-16 study was published in Annals of Oncology6.
The third-generation TKI combined with bevacizumab compared with osimertinib alone was also negative.
Two phase II The findings show that this combination does not work in third-generation TKIs, but instead increases side effects
.

Therefore, we do not currently advocate the combination of third-generation TKIs with bevacizumab
.

⌛ Question 3: Is local treatment for progressive lesions (primary lesions, metastases)? A.
Yes B.
No C.
Unsure of the voting result Pan Yi: I choose C because I think the patient should not receive local radiotherapy at this point in time.
The patient is currently asymptomatic, but he is not sure whether it can be treated locally in the future.
After systemic systemic therapy, there is little residual tumor or oligoprogression after systemic systemic therapy.
Local therapy is feasible at these two time points
.

Lin Jie: I think local treatment can be done
.

Local treatment not only includes radiotherapy, first, local treatment of the chest brings benefits to patients with little progression or little residual
.

Second, local treatment including intrathecal injection, is it considered? Zhang Yongchang: I also choose to perform partial treatment
.

In February this year, Sichuan Provincial People's Hospital published a head-to-head clinical trial 7 in JNCI.
EGFR mutation patients received EGFR TKI + radiotherapy.
The study achieved positive results and the ethics committee terminated the study early
.

Although I personally have three questions about the study, I have written a comment, and the final results have not yet been obtained, but this study suggests that EGFRTKI combined with local therapy is effective
.

At the same time, a study conducted by our director Yang Nong's team included 300 patients, including TKI treatment and immunotherapy patients, and found that radiotherapy was more effective when the lesions were smaller than when the lesions were enlarged
.

The principle of local treatment is that it must be carried out under the condition of stable control of systemic lesions
.

At present, our hospital has given 59 patients intrathecal injection, mainly patients with EGFR mutation, ALK fusion, ROS1 fusion, etc.
The evaluation of the efficiency of intrathecal injection includes imaging, ctDNA and the evaluation scale of patients' thinking ability
.

Although intrathecal injection is valuable, the toxic and side effects are relatively large, and the adverse events are close to 50%, which is worthy of consideration by clinicians
.

Wu Yilong: For this patient, does Director Zhang Yongchang agree to perform intrathecal injection? Zhang Yongchang: At this stage, individuals do not recommend intrathecal injection
.

Thoracic and intracranial lesions can be considered
.

Personally, I think that the patient can now consider radiotherapy for localization, and if the lesion shrinks in the planned re-examination one month later, radiotherapy can be performed
.

Wu Fang: I personally do not agree to partial treatment
.

The patient had two time points of intracranial progression.
The first time a new lesion appeared in the brain.
At that time, the radiologist could easily choose to perform radiotherapy when no targeted drugs were available.
Now, the second time of intracranial progression clearly shows the appearance of T790M.
Mutation, patients have corresponding targeted drugs, and individuals do not recommend intrathecal injection
.

Dong Zhongyi: I choose not to do local treatment
.

At present, an evidence-based medical evidence for whether patients with EGFR mutations should undergo radiotherapy when using TKIs comes from the SINDAS study of Sichuan Provincial People's Hospital.
The study targets patients with oligometastases or less than 5 lesions.
SBRT radiotherapy, combined with TKI, the study achieved relatively good results
.

The patient currently does not have any intracranial symptoms.
Personally, I think the most important thing is to evaluate whether the efficacy of TKI can reach the same effective level as the expected T790 mutation patient.
First, evaluate the control of intracranial lesions and other systemic lesions by osimertinib.
Internal lesions or other lesions such as bone have not been well controlled.
I also agree with Professor Pan's opinion and consider radiotherapy in the future
.

Jiang Mei (Deputy Chief Physician, Department of Medical Oncology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine): I recommend no local treatment.
Just now, Director Zhang Yongchang recommended that the lesions should recede before radiotherapy.
Will patients who are ineffective or progressing after TKI treatment be excluded? outer? At least 8 lesions can be seen from the patient's current CT.
At this time, the radiotherapy doctor is less likely to benefit from the radiotherapy
.

The patient is currently asymptomatic with chest wall bone metastases, PS=1, and local treatment is not recommended
.

Zhou Chengzhi: I think the patient does not need local treatment at this stage, and I agree with Director Pan's opinion that local treatment may be performed in the future
.

Wu Yilong: The SINDAS research was mentioned in the discussion just now.
I would like to hear Director Zhang Yongchang's specific comments on the SINDAS research
.

Zhang Yongchang: First, the design of the SINDAS study is different from the primary endpoint at the time of publication.
The primary endpoint of the study design was PFS.
When the study was published, it was changed to the PFS rate because the endpoint was reached earlier
.

Second, patients with bone metastases accounted for 73% after enrollment in the study, and I personally believe that there is a very large bias in this population
.

Meta-analyses and reviews reported in the literature generally do not exceed 60% of patients with bone metastases
.

Third, the OS of this study was 25.
5 months, compared with several articles published in the same period, the OS was quite different, and the article did not disclose the details of the study
.

Wu Yilong: Dong Zhongyi also paid attention to this research.
What is your opinion on this research? And whether the model can be used in this case? Dong Zhongyi: I mainly focus on the radiotherapy part.
Today, this case does not meet the inclusion criteria of the study.
The SINDAS study has strict control of the lesions, and radiotherapy needs to cover all the lesions before TKI treatment to achieve a synergistic effect, which is equivalent to TKI controlling the whole body.
Radiotherapy was controlled locally, and both PFS and OS in this study achieved good conditions
.

However, in this case, radiotherapy did not cover all the lesions and the lesions were extensive, so I do not recommend the use of the SINDAS study protocol for this patient
.

Wang Zhen (Chief Physician of the Fourth Department of Pulmonary, Guangdong Provincial People's Hospital): The research design of SINDAS is different from other previous studies.
In previous clinical studies, the local treatment of oligometastases was performed after the patient's treatment effect was good.
The first-line patients in this study received local treatment.
For treatment and TKI therapy, the inclusion criteria are no more than 5 total lesions, and it is more challenging to select patients
.

Regarding the local treatment of oligometastases, the key lies in the selection of lesions.
Generally, no more than 5 lesions are recommended.
There are also phase I clinical studies that actively select 10 lesions.
For oligometastases, it is necessary to pay attention to the risk of metastasis in these areas such as meninges, pleural effusion, ascites, bone marrow, and abdominal lymph nodes.
It is suitable for local treatment.
Due to the low probability of radical cure after systemic treatment in these metastases, this patient is currently advised to use osimertinib, which can pass through the blood-brain barrier, and whether local treatment should be considered after the efficacy is evaluated
.

Nie Qiang (Deputy Chief Physician of the Second Lung Department of Guangdong Provincial People's Hospital): In the era of targeted therapy and immunotherapy, tumor surgeons have more opportunities to participate in the treatment of advanced patients
.

For the progression of such advanced patients, when should local treatment of the lesions be involved? The general principle should be that reintervention by the surgeon with systemic disease control may bring the greatest PFS benefit to the patient
.

This patient is currently progressing in an all-round way.
Personally, I think it should be considered from systemic treatment.
The patient is currently asymptomatic, and local treatment can be carried out later, and NGS detection indicates an effective target T790M mutation
.

The follow-up decision on whether to intervene is based on the review after systemic treatment
.

Wu Yilong: At present, there are four international academic views on oligometastasis.
The first is that only a limited number of lesions are oligometastases at the time of diagnosis, usually 3 or less, such as the patients enrolled in the SINDAS study; the second is radical treatment.
The third is oligo-continuation based on systemic treatment, and other lesions are well controlled and only one lesion persists; the fourth is oligo-progression on the basis of systemic therapy, that is, only a limited number of lesions progress, so this patient does not belong to the current category.
these 4 cases
.

The SINDAS study is the pride of China.
It was led by the Sichuan Provincial People's Hospital team and was published in JNCI at the beginning of this year, which attracted many comments, including the comments mentioned by Director Zhang Yongchang.
The biggest question is why these patients have such short OS and PFS? Studies end too early, and patients with EGFR mutations often still have many drug options after their first progression
.

It is hoped that the data can be further supplemented, but the study already tells us that there is a clear benefit of PFS in patients with EGFR mutations who start TKI + local therapy
.

In today's case, the first point, we recommend to immediately switch to the third-generation EGFR TKI 80mg, and evaluate whether it is local treatment after the efficacy evaluation
.

The second point is that although the patient's previous A+T response was very good, there is no evidence to support the continuation of bevacizumab treatment, and the use of bevacizumab is not currently considered
.

Lin Jie: I have a question.
Regarding the combination of osimertinib and bevacizumab, several phase I or phase II studies have been observed, including the WJOG8715L study and the WJOG9717L study.
The first-line use is osimertinib + bevacizumab.
In the second-line use of valizumab, the population included in the study was T790M-positive patients, but the first-line treatment of the included population was purely targeted therapy.
Although the overall PFS and OS benefits were not significant, we also noticed that its IPFS actually achieved multiple benefits.
It is beneficial, should it be considered for patients with obvious cerebral symptoms? The second question, in the case of first-line A+T mode rather than pure targeting, is it meaningful for bevacizumab to cross-line therapy? This also needs to be further explored
.

Wu Yilong: The questions raised by Dr.
Lin Jie are representative.
At present, there is no evidence-based medical evidence to support the efficacy of osimertinib combined with bevacizumab in second-line treatment, but it is now clear that the third-generation EGFR-TKI combined with bevacizumab is effective.
Monoclonal antibodies do not play a synergistic or even antagonistic role.
The first and third generation drugs are different
.

△The above content was recorded from the discussion site and confirmed by the participating experts.
4.
MDT Summary Replace the first-generation EGFR TKI with the third-generation EGFR TKI Ostinib 80mg once a day, and suspend the use of bevacizumab until the efficacy is evaluated Assess whether to add topical therapy
.

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