Sorting out: tumor information source: in recent years, the field of lung cancer treatment has made rapid progress in the live room of lung cancer. Targeted and immunotherapy have achieved remarkable results. Under the guidance of molecular typing, precise treatment has significantly prolonged the survival time of non-small cell lung cancer (NSCLC) patients. There is no doubt that the corresponding targeted drugs are used for the patients with positive driving genes, but there are still many patients who lack clear driving genes, leading to the bottleneck stage of treatment. In addition, the monitoring of NSCLC after radical treatment is particularly important for the prognosis of patients. How to monitor the disease progress of patients reasonably, the American Society of Clinical Oncology (ASCO) guidelines give us relevant suggestions. For this reason, Professor Zhou caicun from Shanghai Pulmonary Hospital Affiliated to Tongji University invited Professor Wang Caixia from Shandong Provincial Hospital, Professor Wang Lifeng from Gulou Hospital Affiliated to Nanjing University Medical College and Professor Zhao Mingfang from the First Affiliated Hospital of China Medical University. He brought the latest relevant literature interpretation on relevant topics Carry out in-depth discussion.
Interpretation of heavy literature in March
According to ASCO guidelines, lung cancer monitoring after radical treatment should be carried out once a half year in the first two years and once a year after two years. In the first two years after treatment, when monitoring the recurrence of imaging, we should use the chest contrast (first choice) or non contrast CT diagnosis which can monitor the adrenal gland; in the first two years after treatment, we should use low-dose screening chest CT when monitoring the new primary lung lesions through imaging. FDG-PET / CT should not be used as a monitoring tool.
Secondly, age should not hinder the imaging monitoring, but it is recommended to consider the health status, chronic diseases and patients' preferences. For patients who are not suitable or unwilling to receive further treatment, imaging monitoring can be ignored.
In addition, clinicians should not use circulating biomarkers and brain MRI as routine monitoring strategies for patients with stage I to III NSCLC or small cell lung cancer (SCLC) undergoing radical treatment. In the first year, the clinician should perform MRI every 3 months and monitor every 6 months in the second year.
The most common subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma. Compared with lung adenocarcinoma, the mutation rate of target related driving genes in squamous cell carcinoma is lower. For these NSCLC patients with negative driving genes, the emergence of anti angiogenic targeted drugs and immunotherapy will undoubtedly bring new hope.
Compass research
Compass was a randomized phase III study of bevacizumab plus pemetrexed in the treatment of advanced non scaly NSCLC. The results showed that the total survival time (OS) of bevacizumab group vs. bevacizumab + pemetrexed was 19.6 months vs. 23.3 months (HR = 0.87), and there was no significant difference between the two groups. Although the compass study is a negative result, we still see that the wild-type EGFR subgroup (92%) has OS benefits after bevacizumab + pemetrexed dual drug maintenance treatment. The OS is 23.3 months, which is close to that of beyond study (24.3 months). At the same time, the PFS of bevacizumab + pemetrexed group was significantly improved. The PFS of bevacizumab group vs. bevacizumab + pemetrexed group was 4.0 months vs. 5.7 months. In addition, safety data are consistent with those reported in previous treatment regimens.
Bevacizumab group vs. bevacizumab + pemetrexed group OS
Wild type EGFR subgroup OS
A review of the ecog-acrin5508 study also suggested that when OS is the primary endpoint of first-line maintenance therapy, the impact of post progression therapy should be considered. The ecog-acrin5508 study ignored the driving gene status, but in fact, for patients with EGFR mutation and ALK gene rearrangement, the OS can be significantly prolonged by second-line treatment.
At this point, when we return to the compass study, we can clearly see the main reasons for the negative results:
·There was no significant difference in OS between the two groups, probably because the OS of the two groups was about 7 months longer than that of the design of compass test;
·In the first-line maintenance therapy, advanced treatment is an important confounding factor in OS analysis. When OS is the primary end point of first-line maintenance therapy, the influence of advanced treatment should be considered.
Keynote-189 research
Keynote-189 latest analysis of the safety and efficacy of first-line treatment of metastatic non scaly NSCLC with pabolizumab or placebo + pemetrexed + platinum. According to the study, the MOS of pabolizumab group vs. placebo group was 22.0 months vs. 10.7 months (HR = 0.56); the MPFs of pabolizumab group vs. placebo group was 9.0 months vs. 4.9 months (HR = 0.48); and the pfs2 of pabolizumab group was better than that of placebo group.
Total population OS
Population PFS
Impower 150 vs keynote-189 liver metastasis subgroup data
The keynote-189 exploratory analysis updated the treatment data of patients with liver and brain metastasis;
In the study, the OS of the experimental group and the control group were 12.6 months vs. 6.6 months (HR = 0.62), PFS (6.1 m vs 3.4 m; HR = 0.52). Compared with the results of the treatment of NSCLC patients with atizumab + bevacizumab + carboplatin + paclitaxel (ABCP) in the study of impower 150, the benefits of OS (13.3m vs 9.4m; HR = 0.52) and PFS (8.2m vs 5.4m; HR = 0.41) of ABCP were higher than those of the combination chemotherapy of pabolizumab, and the risk of death and disease progression was also higher than that of the combination chemotherapy of pabolizumab. The safety of ABCP is the same as that of pabolizumab + chemotherapy. In addition, unlike impower 150, keynote-189 is an exploratory analysis, while impower 150 is a default subgroup, and there is a gap in the level of evidence between the two groups.
Keynote-189 vs. OS, PFS and security analysis of impower 150
Joint guidelines of ASCO and CCO
Finally, we focus on the update of the joint guidelines of ASCO and CCO. In the guideline, patients with non scaly NSCLC with high expression of PD-L1 (TPS ≥ 50%), PS = 0 ~ 1 and no contraindications of immunosuppression checkpoint inhibitors are recommended to use pabolizumab, which can be used with pabolizumab / carboplatin / pemetrexed; for PD-L1 negative (TPS 0%) and low positive (TPS 1-49%), PS = 0-1, no immunosuppression contraindications for non scaly NSCLC patients, we recommend pabolizumab / carboplatin / pemetrexed.
Kcsg-lu15-09 is a multi center, open label, single arm phase II study in South Korea. It aims to evaluate the efficacy and safety of oxitinib in the treatment of NSCLC patients with non classical EGFR mutations. This study is the first prospective study on the treatment of NSCLC patients with nonclassical EGFR mutation with oxitinib. The results show that the response rate of NSCLC patients with nonclassical EGFR mutation treated with oxitinib is high, PFS and Dor are long, and the safety is manageable. 83% of the patients had the first remission after 2 cycles of oxitinib treatment, the median dor was 11.2 months, and 78% of the patients had tumor reduction compared with the baseline. At the end of the data period, the median PFS of oshitini group was 8.2 months; the PFS of L861Q vs. G719X vs. S768I mutation was 15.2 vs. 8.2 vs. 12.3 months. The median OS is not achieved, but the one-year OS rate is good. Although the number of patients evaluated is limited, based on the results of this study, oxitinib can still be used as a treatment option for NSCLC patients with non classical EGFR mutations. However, due to the limited number of each non classical EGFR mutation subtype in this experiment, it is necessary to further study a large number of patients in the future.
Oshitini PFS
Qiang Qiang and Sanren Xing: Interpretation of literature by the big guy
Professor Zhou caicun: first of all, the ASCO guidelines recommend the lung cancer monitoring after radical treatment. Patients in the first two years after treatment should have low-dose spiral CT every six months, but in the actual clinical operation, more domestic doctors will choose chest CT plain scan, tumor markers and other blood related tests, and even increase the frequency of CT examination. However, doctors and scholars in the United States believe that tests that can not reduce the mortality rate of patients, or only bring small benefits to patients, but increase the economic burden, should be selected according to patients' personal wishes. For patients who are not willing to follow-up treatment, or in poor physical condition, there is no need to force follow-up. These ideas are different from our previous ideas. In fact, many examinations are needed for the follow-up of postoperative adjuvant therapy in China, such as CEA, brain MRI, bone scan, abdominal B-ultrasound, color ultrasound, and conventional chest CT, which make the economic burden of patients heavier. Therefore, we can carry out relevant research in China, aiming to explore the impact of 3-month and 6-month examinations on patients' OS, which is worthy of our in-depth consideration.
Secondly, for the patients with negative PD-L1 expression, I will choose bevacizumab + chemotherapy as the first choice. First of all, according to the research data, this kind of patients have achieved a long OS benefit under the treatment of bevacizumab + chemotherapy. Secondly, it is more reasonable from the economic point of view. Finally, it also avoids the greater toxic and side effects brought by immunotherapy. In addition, in the era of immunotherapy, we should pay more attention to the median OS and risk ratio (HR), whether it is single immunotherapy or immunoplus chemotherapy. In the future, long-term survival will also become another major end point of immunotherapy.
Finally, as for the current domestic clinical research, the current research in China is relatively monotonous, and the treatment mode of safety insurance is usually selected to make steady progress, but there is no new idea and no outstanding articles can be published. Therefore, when we carry out clinical research in the future, we must have innovation and dare to break through.
Professor Wang Lifeng: the compass study once again verified the efficacy of anti angiogenic combination therapy for the population with negative driving mutation. Although 92% of the patients included in this study are EGFR wild type, 8% of the patients with other mutation types have become the final result analysis of the uncertainty factors affecting OS in the study. Therefore, other types of gene mutation patients may affect the final OS results in the follow-up results analysis. However, the final subgroup analysis showed that bevacizumab + pemetrexed had better OS data than bevacizumab. This reflects another problem. With the increase of our treatment methods for driving mutation negative population, the OS of patients is also longer and longer, which again confirms the conclusion that OS is affected by the follow-up multi line treatment. As just mentioned in the literature, the OS of the compass study is 23.3 months, which is far more than the OS data of the experiment preset; and compared with the avaperl study, the OS of the compass study is better, which may be due to the fact that 12.5% of the patients in the compass study received the posterior line treatment of immune checkpoint inhibitor (ICIS).
Professor Wang Caixia: first of all, in today's meeting, the research progress of non scaly NSCLC was interpreted, and how to choose bevacizumab + chemotherapy or immunotherapy + chemotherapy for patients with negative driving genes in the era of immunotherapy was introduced, and relevant research data were provided. This will provide better evidence-based medicine for the future clinical practice of how to choose a reasonable anti angiogenesis +, immune + treatment. Secondly, in the era of positive driving genes, theoretically speaking, patients with common sensitive mutation sites will use corresponding targeted drugs. For rare site mutations, we also see a new hope -- oshitinib. Although oshitinib is relatively good, its PFS is still unable to be sensitive