Han Baohui: Year-end inventory of progress in targeted treatment of lung cancer in 2020

Despite the cancellation of major offline meetings in lung cancer such as ASCO, ESMO and WCLC in 2020 due to the outbreak of neo-crown pneumonia, there are still a number of major studies this year that have been published.
the author on this year's lung cancer field targeted treatment progress inventory, with colleagues to share.
01 EGFR path to open the frontier, the gate forward target treatment took the lead in the treatment of advanced lung cancer, after more than 10 years of development, targeted treatment has become the first line of non-surgical advanced lung cancer priority treatment strategy.
recent years, targeted therapy has gradually moved towards middle and late stage lung cancer, so the second peak of research related to postoperative ancillary therapy, including EVAN, ADJUVANT and ADAURA, are representative studies.
year, several studies have been revealed with mixed results.
When the data were first published in the ADJUVANT study, the mid-range DFS in the targeted therapy and chemotherapy groups was 28.7 and 18.0 months, respectively, and receiving targeted therapy reduced the risk of disease progression by 40%, making targeted therapy one of the options for postoperative ancillary therapy.
However, at this year's ASCO annual meeting, the ADJUVANT study published final OS data, after a medium of 76.9 months of follow-up, the target treatment group and chemotherapy group of the middle OS of 75.5 months and 79.2 months, respectively, the difference is not statistically significant, which means that patients immediately after surgery to receive 2 years of targeted treatment and first receive standard treatment, disease recurrence and then targeted treatment, the two treatment models of the efficacy does not exist.
, the timing of a generation of EGFR-TKI interventions in this segment of patients is currently controversial.
generation of drug treatment failed, but the three generations of drug postoperative auxiliary treatment is "willow dark flowers and another village."
ADAURA study explores the position of three generations of drugs in postoperative ancillary therapy.
the ADJUVANT study, which allowed patients to be admitted to the group after chemotherapy for a period of three years, and the study included patients with phase IB.
showed that Oghidini reduced the risk of disease progressity by 83 percent, and that even in the IB population, HR was close to 0.4.
data were released, 1% and 10% of patients in both groups had relapsed central nervous system diseases, respectively.
can reduce the risk of intracranial transfer or recurrence by up to 82%.
this outstanding research, the study successfully reached the new England Journal of Medicine.
and the patient's final OS is to be expected.
: Surprise and Surprise There are now several mature products for generation/second/generation three drugs, so the development of new drugs has passed the initial.
how to improve the effectiveness of existing therapeutic "weapons" through reasonable matching and "platooning" is a hot topic this year.
, a small sample exploratory study initiated by the author's team analyzed the efficacy and safety of erotinie and atrotinie.
60 patients in the study group, 25% had brain metastasis baseline, and 56 patients formed an intentional analysis population.
data show that the group of patients ORR reached 91.1%, DCR reached 100%, 20-month PFS rate of 56.75%, the medium PFS has not yet reached.
the preliminary data, this treatment strategy is very promising, which gives us an unexpected "surprise."
this year's ESMO annual meeting, our scholars published a similar combination, Apatinib United Gifeitinib, which showed that joint apatinib reduced the risk of disease progressity by 30 percent.
, OS data from both studies has not yet been published, and it is expected that the benefits of PFS will translate into OS benefits, often unexpected in treatment strategies that are combined with vascular targeting.
this year's ANNUAL ASCO meeting, the NEJ-026 study published final OS data, which showed that 25.9% and 23.2% of patients in the combined and single-drug groups received oxytinib as a backline treatment after progression, with the middle OS in both groups receiving 50.2% For 7 and 46.2 months, the difference was not statistically significant (HR=1.00; 95%CI:0.68-1.48), which is almost consistent with the data from the JO25567 study published in 2018.
addition to the combination with internal medicine therapy, and radiotherapy and other treatments to reflect the multidisciplinary comprehensive treatment of research has also brought "China surprise."
as this year's ASCO Annual Meeting, the SINDAS study brought by Chinese scholars once again provides high-level evidence-based medical evidence for joint topical therapy.
found that patients with combined topical therapy had a medium PFS of 20.2 months, which was more than three generations of drugs in value, and that the risk of disease progression was 39 percent lower than in patients who received only one generation of medication.
but not all of them can achieve "good couples", some strong union did not have the desired effect, and the results of some studies were even "surprising".
year's ESMO Annual Meeting, scholars from Japan announced the efficacy and safety of Oghithini±Bevaded single-drug treatment for patients with the access to the T790M mutation.
study found that combined beva beading increased the risk of disease progression by nearly 1.5 times, with the medium PFS in the combined treatment group and the single-drug oxytinib group at 9.4 months and 13.5 months respectively (HR=1.44,95% CI 1.00-2.08, P-0.20), the two groups of the middle OS did not reach and 22.1 months (P-0.96), only ORR in the combined treatment group is better, the two groups are 68% and 54%, respectively.
addition, there are also studies to explore the first-line treatment of patients with advanced NSCLC.
one-armed exploratory study, published in May this year in JAMA Oncology, included 49 patients who received the treatment, with a medium PFS of just 19.0 months, no better in numerical terms than the 18.9 months of oghithinib.
So, from the available data, the three-generation drug combined beva bead monoantin does not appear to show the expected efficacy, and the combined chemotherapy FLAURA-2 study is currently under way, from this year's ESMO Asia just published the pre-import data, patients are well-to-resist, there is no unexpected safety events.
also been conducted in patients with secondary T790M mutations with remolu monoantigen and oghithini, another vascular-targeted drug of monoclonal antibodies.
in the Phase I study, which included 25 patients, ORR was 76 percent for two full-dose medications, with a medium PFS of 11 months, and 67 percent, 50 percent and 20 percent of 24 months of PFS for 6, 12 and 24 months, respectively.
had brain transfer and brainless metastasis at baseline, the medium PFS was 14.7 months and 10.9 months, respectively.
considering that this is only a small sample exploratory study, the patient's benefits need to be further confirmed.
02 ALK Pathway This year, the brightest on the ALK pathway was the release of data on the first three-generation ALK-TKI-Lauratinie first-line application, while the results of the study of the domestic second-generation drug Ensartini were also disclosed at the WCLC pre-conference meeting.
the published data, both drugs showed good therapeutic results.
CROWN study, published at this year's ESMO annual meeting, compared the efficacy and safety of loratini and cytocinone.
this is the first time the study has disclosed data.
The main study endpoints for the study were PFS assessed by the Independent Review Board, the Lara tinist and kerotinie groups were not reached and 9.3 months, respectively, and the secondary study endpoint was PFS assessed by the researchers, with the two groups not reaching and 9.1 months, respectively, and the HR group 0.21.
72% and 56% respectively in the two groups of 3 degrees and above.
eXalt3 study data released at the WCLC pre-conference showed the efficacy of the domestic second-generation drug ensartini, with equally good results.
In this study, Nsatini showed a full range of advantages over clotini, with the two groups showing a medium PFS of 25.8 months and 12.7 months, respectively, ORR of 75% and 67%, intracranial response rates of 64% and 21%, respectively, and intracranial progression rates of 4% and 24% respectively in the first year.
At present, the ALK path has formed a generation of the drug cytocininib, the second generation of the drug ceretinib, alethinib, bugtinib, Nsatini and the third generation of the drug Lara tinib "three with the same" situation, in the targeted treatment of the addition of patients with the middle OS for more than 7 years, has been the first to enter the lung cancer "slow disease" management era.
But the author also noted that even if a small number of patients receive a variety of targeted treatment, the middle OS compared with the overall population there is still a large gap, clarifying the molecular mechanism and optimizing the treatment strategy of this part of the patient is a problem worth exploring in the future.
03 Rare Mutations - As the competition between the EGFR and ALK pathfage heats up, research into rare/rare mutations has broken new ground and several excellent therapeutic drugs have emerged.
RET Pathloxo-292 and BLU-667 are two targeted drugs for RET rearration, and the efficacy and safety data presented by both drugs at this year's ASCO annual meeting are impressive.
in the LIBRETTO-001 study, the ORR of treated patients reached 70%, the medium PFS reached 18.4 months, the 1-year PFS rate was 68%, and the medium PFS of primary treatment patients has not yet been reached.
addition, the drug also has a good ability to pass through the blood-brain barrier, intracranial ORR up to 91%, the central nervous system response duration of 10.1 months.
from the efficacy data, almost the same as the EGFR pathway three generations of TKI.
can say that this part of the patient really ushered in the era of efficient, low-toxic targeted treatment.
, research on the drug resistance mechanisms of the next generation of RET-TKI is being carried out simultaneously.
A study published In the Analgamology of Oncology on September 29 found that secondary mutations in the RET tyrosine kinase domain led to RET-TKI drug resistance in some patients, but the frequency of mutations was low, with the vast majority occurring at the G810 bit, including G810S mutations and G810C mutations;
, published at the same time in the same period, found that for patients with MET amplification, the drug resistance was further overcome with ret-TKI therapy.
patients with met No. 14 exon jump mutation of about 3-4% carried met No. 14 exon jump mutation.
this year, three promising drugs, Carmatini, Ticpotini and Sevotini, published efficacy and safety data.
geometry multi-queue study explored the efficacy and safety of carmaticiniry in treating this group of patients.
data show that in patients treated and first-time patients, the ORR of carmatini is 41% and 68%, respectively.
PFS was 5.4 months and 12.4 months, respectively, showing better results in this group of patients, especially in primary treatment patients.
However, in patients with MET amplification, the treatment results were not ideal: in patients with amplification multiplies greater than 10, ORR in both treated and primary patients was 29% and 40%, respectively, below the preset lower limit, with a medium response duration of 8.3 months and 7.5 months, respectively; In patients with multiples of 6-9, ORR was 12%, in patients with an amplification multiple of 4-5, or 9%, in patients with an amplification multiple of less than 4, or 7% in ORR, the medium PFS in the three groups was 2.7 months, 2.7 months and 3.6 months, respectively.
, in clinical practice, met amplification was > of NSCLC patients with 10.
, more efficient treatments are needed for patients with MET amplification.
is another targeted treatment for the met No. 14 exon jump mutation.
its research data at this year's ASCO annual meeting.
note that while the study was only presented in the ASCO annual meeting, it was published simultaneously in the New England Journal of Medicine.
data showed that the independent review committee assessed PFS for 8.5 months, the medium PFS for patients in the liquid biopsy and tissue biopsy group was 8.5 months and 11.0 months, respectively;
11 patients with brain metastasis, the independent review board assessed ORR at 55 per cent, response duration at 9.5 months and PFS at 10.9 months.
therefore, from the available data, thypolytinist has a good role through the blood-brain barrier.
the treatment of the HER path into the mutation HER2 path in recent years has made few breakthroughs, especially the insertion mutation is a "big problem" in the field of targeted therapy.
recent studies offer hope for targeted treatments for this path.
July of this year, a Phase II study on the late NSCLC treatment of HER2 mutations with the domestic drug pyridoxine, led by Chinese scholars, was published in Journal of Clinical Oncology.
note that in this study, some patients were severely treated and about 80 percent carried insertion mutations.
this, or 30% ORR in the whole group, with a medium PFS of 6.9 months, a 12-month PFS rate of 22.5%, a medium OS of 14.4 months and a 12-month OS rate of 69.1%, created new treatment hopes for patients.
two more needles