*For medical professionals reading only, please refer to
1-story summary
A situation that all patients with advanced EGFR mutant non-small cell lung cancer (NSCLC) have to face, which is the problem of TKI drug resistance! Faced with this difficulty, all patients who have undergone first- or second-line treatment of TKI, the National Comprehensive Cancer Network (NCCN) guidelines recommend: If the patient has a T790M mutation, third-generation TKI osimertinib is recommended; if patients do not have T790M mutation or osimerresistant, standard chemotherapy treatment is recommended. Unfortunately, platinum-based chemotherapy has a median progression-free survival (PFS) of only about 4 or 5 months, and its efficacy is very limited! However, with the continuous development of research, immunotherapy has finally entered the process of driving gene-positive NSCLC! Results of Phase II study of O-drug Vs O+Y for treatment of EGFR-TKI-resistant NSCLC
NCT03091491 is a randomized phase II clinical trial conducted at three clinical centers of Singapore . Nivolumab (O-drug) VsO drug combined with ipimumab (Y drug) treats EGFR-TKI-resistant EGFR mutation NSCLC. Patients in single-drug group are allowed to cross to the co-drug group when disease progression occurs. Randomized stratification factors are PD_L1 expression and brain metastasis. The primary study endpoint was total effective, while the secondary study endpoints included progression-free survival, overall survival, and safety.
Between April 2017 and December 2018, 31 patients with advanced NSCLC were included, with PDL1 expression: 45.2% <>
results show that the median follow-up time of
was 24.3 months, and as of June 2019, the clinical ended early, all patients had stopped the drug.
30 patients are available for evaluation, and only one patient in the co-pharmacy group has partial remission. The total effective efficiency of the O-drug group was 0%, the disease control rate was 40%, and the median progression-free survival was 1.31 months. Four patients crossed to the co-drug group, but none of them responded. The total effective efficiency of nivolumab combined with ipilimumab was 6.3%, the disease control rate was 43.8%, and the median progression-free survival was 1.18 months. The median overall survival of all patients was 5.65 months. Among the 16 patients with brain metastasis, 6 cases experienced progression of brain lesions, and 13 cases experienced worsening of brain symptoms.
02 Tirelizumab combined with chemotherapy to treat targeted drug-resistant EGFR+NSCLCh
study included patients who had not undergone systemic chemotherapy, had disease progression and was confirmed to be T790M negative after first-generation EGFR-TKI, or patients who were positive for T790M but further progressed after third-generation EGFR-TKI treatment, or 40 patients with EGFR-TKI who had no systemic chemotherapy, had disease progression after first-line treatment, del There were 21 cases of 19 mutations, 17 cases of L858R mutations, 1 case of G719X and other EGFR mutations, 8 cases of brain metastasis (20%), 92.5% had used 1 or 2 generations of EGFR-TKI, 55% had used 3 generations of EGFR-TKI, 47.5% had used 1/2 generations of EGFR-TKI, and 37.5% had used antiangiogenic drugs before. . Patients were given tirelizumab + albumin paclitaxel + carboplatin treatment, and one-year progression-free survival was the primary study endpoint, and the secondary study endpoints included objective effective efficiency (ORR), disease control rate (DCR) and safety.
results showed that the objective effective efficiency of 32 patients was 59.4%, DCR was 90.6%, median to remission time of 80 (range 41-93) days, median progression-free survival and overall survival were still immature. As of July 13, 2021, 26 patients continued to be treated in the group. The ORR of EGFR del 19 mutation in
17 was 59.4%, and the DCR rate was 88.2%, while the ORR of 14 L858R mutations was 42.9%, and the DCR was 92.9%, but there was no significant difference. In terms of safety, the proportion of adverse reactions related to treatment at level 3 or above is 32.5%, serious adverse reactions are 17.5%, and 7.5% of patients stop taking medication due to adverse reactions.
03 A multicenter retrospective study on the treatment of advanced NSCLC with ATINLIZUB + bevacizumab + chemotherapy for the treatment of driver gene positive NSCLC4
AsterisiZUB + bevacizumab + paclitaxel or pemetrexed for the treatment of advanced NSCLC.
Between July 2015 and July 2021, the study included 97 advanced NSCLC, with median age 60 years old, 95% adenocarcinoma, 47% brain metastasis, 13% leponema metastasis, and 36% liver metastasis. There were 68 cases of EGFR+, 4 cases of ALK fusion, 10 cases of KRAS mutation, 2 cases of RET fusion and 2 cases of METex14 jump mutation.31 of the 68 patients with EGFR mutations had previously received osimertinib treatment.
53 patients received atelizumab + bevacizumab + carboplatin + paclitaxel, and 43 patients received atelizumab + bevacizumab + carboplatin + pemetrexed.
Among the 73 patients who can be evaluated, ORR 59%, DCR 85%, median PFS5.4 months; ORR 57%, DCR 82%, median PFS5.1 months in patients with EGFR mutation (51 cases), ORR 57%, DCR 82%, median PFS5.1 months in patients with brain metastasis (35 cases), ORR 60%, DCR 83%, median PFS5.8 months in patients with leponema metastasis (12 cases), ORR 42%, DCR 84%, median PFS4.3 months in patients with liver metastasis (28 cases), ORR 64%, DCR 85.5%, median PFS5.1 months.
ITT population, median overall survival (OS) was 8.85 months, median OS was 8.1 months in patients with brain metastasis, median OS was 5.7 months in patients with leponema metastasis, median OS was 8.6 months in patients with liver metastasis, and median OS was 7.6 months in patients with EGFR mutation.
34% of patients need to reduce the dose of chemotherapy drugs. Pemetrexed is better tolerated compared to paclitaxel, and the reduction ratio is lower. Five patients terminated bevacizumab due to colon obstruction, jaw osteonecrosis, proteinuria, renal dysfunction and hemoptysis. One patient was terminated due to allergic reactions and two patients were terminated due to immune-related adverse reactions, atelizumab. Two patients died of gastrointestinal perforation.
04 Xindili combined program for the treatment of EGFR targeted drug resistance
2021 European Association for Oncology Asian Annual Meeting (ESMO Asia), the latest data of the ORIENT-31 study was released. This is the first time that the results of the interim data were released! The immunocompromised regimen in the study performed very well, significantly prolonging median PFS. Compared with the chemotherapy group, median PFS of : 6.9 months vs 4.3 months ! The meeting of
showed that the third phase of ORIENT-31 study has reached its main endpoint. This study was designed to evaluate the effectiveness and safety of sindilizumab combined with or without IBI305 and chemotherapy in patients with EGFR-TKI progressing treatment with EGFR-TKI.
A total of 444 patients were included in this study, all of whom were EGFR positive locally advanced or metastatic non-squamous NSCLC, which were divided into three conditions:
(1) The first and second generation EGFR TKI treatment progressed and T790M was negative;
(2) The first and second generation EGFR TKI treatment progressed after the first and second generation EGFR TKI treatment progressed and the third generation EGFR TKI treatment progressed;
(3) The first line of treatment progressed.
researchers randomly enrolled the patients in 1:1:1 and divided into 3 groups:
A group: Xindilizumab + IBI305 + pemetrexed + cisplatin;
B group: Xindilizumab + placebo + pemetrexed + cisplatin;
C group: two placebo + pemetrexed + cisplatin.
The main research endpoint is PFS evaluated by IRRC according to the RECIST v1.1 standard, and the secondary research endpoints include OS, PFS, ORR and security evaluated by the investigator according to the RECIST v1.1 standard.
In the intention-to-treat (ITT) population, median PFS of Xindilizumab combined with bevacizumab + chemotherapy vs chemotherapy: 6.9 months vs 4.3 months (HR=0.464, 95% CI: 0.337-0.639, P<0.0001).>
ORR of with sindilizumab combined with bevacizumab + chemotherapy regimen was 43.9% , while that of only 25.2% in the chemotherapy group; there was no significant difference in the median duration of remission (DoR), which was 8.3 months and 7 months , respectively.
security, there is no new security signal. The most common (≥25%) adverse events of during treatment (TEAE) include anemia, decreased neutrophils, loss of appetite, decreased leukocytes, nausea, and weakness; the most common (≥2%) immunotherapy -related adverse events (irAE) include hypothyroidism, hyperthyroidism, etc.
05 Pembrolizumab: Immune combined with chemotherapy to attack driver-positive tumors
Phase II clinical study (NCT03242915) explored the efficacy of pembrolizumab (K drug) + pemetrexed + carboplatin in the treatment of driver-positive NSCLC patients.The study included 33 recurrent NSCLC patients who had received targeted therapy, including 26 cases of EGFR mutation (median age 68 years old, 74% female, 65% white, 46% brain metastasis, 61% had received first-line treatment, 39% had received second-line treatment, 85% had osimertinib), and 7 cases of ALK fusion (median age 66 years old, 57% female, 86% white, 28% had brain metastasis, 71% had received first-line treatment, and 29% had received second-line treatment). The patient received K drug (200mg) + pemetrexed (500mg/m2) + carboplatin (AUC5) every three weeks. After four courses of treatment, K drug + pemetrexed was maintained for two years.
results show that EGFR subgroup ORR is 42.3%, median PFS is 8.3 months, median OS is 22.2 months; ALK subgroup ORR is 28.6%, median PFS is 2.9 months, median OS is 2.9 months.
In terms of safety, the most common (≥15%) adverse reactions are fatigue, nausea, vomiting, skin toxicity, elevated AST/ALT, diarrhea, etc. The incidence of adverse reactions above grade 3 was low, including 1 case of grade 3 pneumonia, 1 case of grade 4 elevated creatinine and 1 case of type 1 diabetes.
In short, in this study, it can be seen that in this study, the use of K-drug combined regimen for EGFR-positive patients can still achieve good therapeutic effects. For patients with no drugs available in the backline, there may be potential treatment options. The ALK re-arrangement cohort included only 7 patients, and the patients progressed rapidly, with median PFS and OS only 2.9 months, but it may also be because of the small number of patients.
resistance is inevitable for targeted treatment. For NSCLC patients with positive driver genes, appropriate combination regimens are selected for use in immunotherapy drugs in the backline; different mutant genes have different effects on immunotherapy. Judging from the existing data, EGFR patients have higher response rates to immunotherapy than patients with ALK fusion NSCLC.
We are pleased to see the significant progress made by immunotherapy in patients with driver gene-positive NSCLC, and should also be used cautiously in clinical practice. We look forward to large-sample randomized controlled studies to provide more clinical evidence.
Statement: The information involved in this material is for reference only. Please follow the opinions or guidance of doctors or other medical and health professionals.
This article is first published: Find Medicine Book
Author: Yi'an Medical Department
Editor: Sweet
*The medical community strives to ensure the accuracy and reliability of the published content when it is approved, but does not make any commitments and guarantees for the timeliness of the published content, as well as the accuracy and completeness of the cited materials (if any), and does not assume any responsibility arising from the outdated content, the possible inaccuracy or incompleteness of the cited materials. Please check separately when using this or using it as the basis for decision-making.
Copyright Statement
Reprint of this article If you need to reprint, please contact authorization
- End -
