Metz inventory: ten major advances in lung cancer in 2021

Collection: Top Ten Progress in 2021

Collection: Top Ten Progress in 2021 Top Ten Progress in 2021

For lung cancer in 2021, although some of the main ideas in the past will continue as a whole, there are also many breakthroughs, including some breakthroughs in the treatment of rare targets
.

At the same time, KRAS, as well as new types of therapeutic drugs such as immune enhancers, have also achieved initial results

1.
KRAS inhibitors have achieved initial success in lung cancer

1.
KRAS inhibitors have achieved initial success in lung cancer

KRAS mutation is a common mutation type of NSCLC, and the incidence is higher in lung adenocarcinoma, about 25% to 30%.
The most common mutation site is G12C (39%), followed by G12V (21%), G12D (17 %)
.

In recent years, small molecule TKIs that directly target the KRAS protein have been developed and entered clinical research

Sotorasib (AMG 510) is an inhibitor of KRAS G12C mutant protein, which irreversibly binds to the cysteine ​​12 (G12C) of mutant KRAS protein to inhibit downstream pathways
.

The ASCO annual meeting in 2021 announced the latest data from the Phase II CodeBreaK100 study of AMG 510 for the treatment of KRAS G12C mutant NSCLC ^[14] .

ASCO ^[14]

The WCLC annual meeting in 2021 reported the baseline brain metastasis subgroup data of the CodeBreaK100 study ^[15] .
The median PFS of patients with baseline brain metastasis was 5.
3 months, and the median OS was 8.
3 months; in 16 evaluable brains In patients with metastases, the intracranial DCR was 88% (14/16)
.

In addition, the WCLC 2021 annual meeting also reported the preliminary results of the exploratory analysis of the CodeBreaK100 study ^[16] .

^{[15] [16]}

The KRAS inhibitor JDQ443 has initially shown potential anti-tumor activity in preclinical studies
.

Currently, a global open multicenter Phase Ib/II study of JDQ443 dose escalation in patients with advanced solid tumors with KRAS G12C mutations is underway

2.
Research on the benefit of adding immunotherapy to adjuvant chemotherapy

2.
Research on the benefit of adding immunotherapy to adjuvant chemotherapy.
Research on the benefit of adding immunotherapy to adjuvant chemotherapy

IMpower010 study: is a randomized, open-label global multicenter phase III clinical study to explore the benefits of adding atelizumab to adjuvant chemotherapy
.

The study included 1,280 patients with completely resected stage IB-IIIA NSCLC and ECOG PS 0-1 who received cisplatin chemotherapy (plus pemetrexed, docetaxel, gemcitabine or vinorelbine).

Research design

Research design

Baseline characteristics

Research results: DFS in PD-L1 TC≥1% stage II-IIIA (HR [95% CI] 0.
66 [0.
50, 0.
88]) and all randomized stage II-IIIA (HR 0.
79 [0.
64, 0.
96]) patients have significant DFS Sexual borders cross
.

In all randomly assigned stage II-IIIA patients, as the expression of PD-L1 increased, an improvement in DFS was observed [TC <1%, 0.

Research results: DFS in PD-L1 TC≥1% stage II-IIIA (HR [95% CI] 0.

3.

The results of the study showed that the study included 219 EGFR and ALK-negative NSCLC patients with ECOG PS 0-1 who randomly received OSE2101 subcutaneous Q3W treatment for 6 cycles at 2:1, followed by Q8W for 1 year, Q12W until progress, and standard treatment (more Sitaxel or Pemetrexed Q3W) comparison
.
The primary endpoint of the study was OS, and the secondary endpoints were DCR and quality of life QoL
.

Quality of Life

The OS of the OSE2101 group vs the standard treatment group was 11.
1 and 7.
5 months, respectively [HR 0.
59 (0.
38-0.
91) p = 0.
02]
.
The 6-month DCR was 25% vs 24% (NS), the mPFS was 2.
7 months vs 3.
4 months (NS), and the ORR was 8% vs 18% (p=0.
07)
.

In the OSE2101 group vs.
the standard treatment group, the survival time after progression was 7.
7 months vs 4.
6 months [HR 0.
46 p=0.
004], and the ECOG PS deterioration time was 8.
6 months vs 3.
3 months [HR0.
45 p=0.
0005]
.
The QoL global health status of OSE2101 remained unchanged (p<0.
05)
.
Serious adverse events were 38% and 68% (p<0.
001)
.
Compared with standard treatment, OSE2101 has good benefits/risks in patients with advanced HLA-A2+ NSCLC
.
In patients with secondary resistance to immune checkpoint inhibitors, the HR of OS improved from 0.
86 to 0.
59, and the median OS of OSE2101 increased significantly by 3.
6 months
.

4.
Application of immunopotentiator in the treatment of lung cancer

4.
Application of immunopotentiator in the treatment of lung cancer

Results of the study: Compared with the docetaxel group alone, the average OS of the Pranabrin combined with docetaxel group was 15.
08 months vs 12.
77 months, and the median OS was 10.
5 months vs 9.
4 months, with 24 The monthly OS rate (22.
1% vs 12.
5%), 36-month OS rate (11.
7% vs 5.
3%), and 48-month OS rate (10.
6% vs 0%) show that the combined regimen has long-lasting anti-cancer benefits
.

The average PFS was 6.
0 months vs 4.
4 months, the median PFS was 3.
6 months vs 3.
0 months, the ORR was 12.
23% vs 6.
76%, and the incidence of grade 4 neutropenia was significantly reduced (8th in the first course of treatment) Day: 27.
8% vs 5.
26%; Day 8 of the entire course of treatment: 33.
58% vs 5.
13%)
.
In terms of safety, the combined treatment group was well tolerated, and the quality of life of patients was better than that of the control group
.

5.
The dual-target plan consisting of dabrafenib and trametinib is used for BRAF V600E in the treatment of lung adenocarcinoma, written in guidelines

5, double target scheme tadalafil Nepalese joint Qumei consisting of imatinib for the treatment of BRAF V600E in lung adenocarcinoma, written guidelines Guide

The latest Chinese population epidemiological data released at the WCLC annual meeting and ESMO annual meeting in 2021 show that the incidence of BRAF gene mutations is about 1.
78% to 3.
15% [5,6], among which BRAF V600E is the most common in lung adenocarcinoma
.
At present, the dual-target plan (D+T plan) composed of dabrafenib and trametinib has become the priority recommendation of guidelines (including NCCN guidelines, ESMO guidelines and CSCO guidelines)
.

Figure 2 Recommendations for BRAF V600 mutant lung cancer treatment guidelines

Lung cancer

The recommendations of the guidelines are based on a phase II clinical trial called BRF113928.
The recently updated data showed that newly-treated and treated advanced BRAF V600E mutant NSCLC patients treated with dabrafenib combined with trametinib had an ORR of 63.
9, respectively.
% And 68.
4%, the median PFS was 10.
8 months and 10.
2 months, and the median OS was 17.
3 months and 18.
2 months, respectively
.

NSCLC

ESMO 2021 reported a real-world study that included 63,051 patients [8].
Compared with the median OS of 24.
6 months in the overall population in the BRF113928 study, dabrafenib combined with trametinib demonstrated in the real world A longer survival benefit (29.
3 months)
.

.
6, the MET inhibitors popping, Capmatinib, Tepotinib, and Savolitinib treatment efficiency continuously disclosed

.
6, MET inhibitors popping, Capmatinib, Tepotinib, and Savolitinib treatment efficiency continuously disclosed MET inhibitors popping, Capmatinib, Tepotinib, treatment and Savolitinib

The effects of traditional chemotherapy and immunotherapy for patients with MET ex14 jumpers are not good.
In recent years, MET inhibitors have been reported frequently, and Capmatinib, Tepotinib, and Savolitinib have been approved for marketing
.
Capmatinib has an ORR of 68% for the first-line treatment of MET ex14 jump mutations.
It is currently the most effective targeted drug for the treatment of MET ex14 jump mutations and has excellent intracranial control
.
At the same time, the ORR of the first-line treatment is higher than 40.
6% of the second-line treatment, so it is recommended to use it as soon as possible
.
In addition, the efficacy and safety of Tepotinib in elderly patients have been confirmed
.
Amivantamab has also been explored in MET ex14 jumping mutations and has shown good efficacy.
MET ex14 jumping mutations may add new drugs
.

immunity

The updated data of the MET ex14 skip mutation cohort of the GEOMETRY mono-1 study showed that the ORR of patients receiving Capmatinib first-line treatment (n=28, cohort 5b) was as high as 67.
9%, the median DOR was 11.
14 months, and the median PFS was 12.
4 months.
Bit OS reached 20.
8 months
.
The ORR of patients receiving Capmatinib second-line treatment (n=69, cohort4) was 40.
6%, the median DOR was 9.
7 months, the median PFS was 5.
4 months, and the median OS was 13.
6 months
.

The results of the subgroup analysis of the VISION study showed that Tepotinib showed similar efficacy and safety in subgroups divided by age (<75 years and ≥75 years)
.
The VISION study enrolled a large number of elderly NSCLC patients with MET ex14 jumping mutations.
The ORR of the population less than 75 years old (n=157) was 52.
2%, and the disease control rate (DCR) was 74.
5%; those of the population ≥75 years old (n=118) ORR was 44.
9%, and DCR was 75.
4%
.

The preliminary results of the CHRYSALIS study showed that Amivantamab showed anti-tumor activity in patients with MET ex14 skip mutation NSCLC, 64% (9/14) of evaluable patients had partial remission, and the median treatment time was 6.
5 months
.

7.
The efficacy data of Selpercatinib and Pratinib in RET fusion patients are impressive

7.
The efficacy data of Selpercatinib and Pratinib in RET fusion patients are impressive

The incidence of RET rearrangement in NSCLC is about 1%~2%, and it is common in young, non-smokers with lung adenocarcinoma
.
Many internationally listed RET-TKIs include Vandetanib, Cabozantinib, Selpercatinib (LOXO-292) and Pratinib (BLU-667)
.
Among them, pratinib (BLU-667) has been approved for listing in China this year
.

The LIBRETTO-321 study reported at the WCLC 2021 annual meeting brought data on the Chinese population of Selpercatinib
.
This is a phase II clinical study conducted in China.
Among 47 RET fusion-positive patients, the ORR of the newly treated patients was 90%, and the ORR of the treated patients was 58.
3%
.
This is consistent with the results of the LIBRETTO-001 study previously reported
.

The ARROW study for pratinib is a global phase I/II clinical study.
The WCLC 2021 will announce the Chinese cohort data of the ARROW study.
The ORR of patients who have received chemotherapy in the past was 66.
7%, and the DCR was 93.
9%; The ORR of untreated patients was 80%, and the DCR was 86.
7%
.
The efficacy results observed in the Chinese population are consistent with the efficacy results of the global population previously reported in the ARROW study
.

8.
Multiple HER2 inhibitors have achieved breakthroughs in curative effect in NSCLC

8.
Multiple HER2 inhibitors have achieved breakthroughs in curative effect in NSCLC

In NSCLC, HER2 gene mutations are manifested as gene amplification and mutations.
The 20 exon insertion mutation (HER2 exon20) is the most common.
3% of NSCLC patients have HER2 gene mutations
.
The current NCCN guidelines only recommend antibody-conjugated drugs to treat HER2-positive NSCLC patients, including T-DM1 and DS-8201
.

In NSCLC, HER2 gene mutations are manifested as gene amplification and mutations.
The 20 exon insertion mutation (HER2 exon20) is the most common.
3% of NSCLC patients have HER2 gene mutations
.
The current NCCN guidelines only recommend antibody-conjugated drugs to treat HER2-positive NSCLC patients, including T-DM1 and DS-8201
.

DESTINY-Lung01 is a multi-center phase II clinical study evaluating DS-8201 for HER2 overexpression and HER2 mutation advanced NSCLC patients.
ESMO 2021 will announce the data of the HER2 mutation cohort, with ORR reaching 54.
9% and DCR reaching 92.
3% , The median PFS was 8.
2 months, and the median OS was 17.
8 months
.
It showed activity in patients with different HER2 mutation subtypes .

The 2021 ASCO Annual Meeting reported the phase II clinical study data of pyrrotinib combined with apatinib in the treatment of 33 patients with HER2 mutant NSCLC.
The overall median PFS was 6.
8 months, and the median OS did not reach; baseline brain metastases patients The ORR of patients without brain metastasis was 46.
2% (6/13), the ORR of patients without brain metastasis was 45.
0% (9/20), the ORR of patients with second-line therapy was 47.
1% (8/17), and the ORR of patients with third-line and above was 43.
8% (7 /16)
.

Another phase II clinical study reported by ASCO showed that the triple therapy of trastuzumab, pertuzumab and docetaxel in patients with advanced HER2-mutant NSCLC had an ORR of 28.
9% and a duration of remission (DOR) of At 11.
0 months, the median PFS was 6.
8 months, and the median OS was 17.
6 months
.

ESMO reported the preliminary data of Poziotinib in the treatment of 48 cases of untreated HER2 exon20 mutant NSCLC.
The ORR was 43.
8%, the DCR was 75%, and the median PFS was 5.
6 months
.

9.
The final safety analysis, main research endpoints and updated efficacy results of pembrolizumab for neoadjuvant treatment of early NSCLC

9.
The final safety analysis, primary research endpoints and updated efficacy results of pembrolizumab for neoadjuvant treatment of early NSCLC.
Final safety analysis, primary research endpoints and primary research endpoints of pembrolizumab for neoadjuvant treatment of early NSCLC Updated efficacy results

The results of the study showed that pembrolizumab was used for neoadjuvant treatment of early NSCLC, with an MPR rate of 27%, a pCR rate of 12%, and a grade 3 to 4 TRAE rate of 8%
.
RP2D/S recommends injection of two doses of pembrolizumab neoadjuvant therapy at three-week intervals, followed by surgery two weeks later
.
A longer interval from treatment to surgery is associated with a higher MPR rate
.

The results of the study showed that pembrolizumab was used for neoadjuvant treatment of early NSCLC, with an MPR rate of 27%, a pCR rate of 12%, and a grade 3 to 4 TRAE rate of 8%
.
RP2D/S recommends injection of two doses of pembrolizumab neoadjuvant therapy at three-week intervals, followed by surgery two weeks later
.
A longer interval from treatment to surgery is associated with a higher MPR rate
.

10.
Small cell lung cancer is progressing slowly, D + EP is used as the standard treatment for extended stage SCLC (CASPIAN study)

10.
Small cell lung cancer is progressing slowly, D + EP is used as the standard treatment for extended stage SCLC (CASPIAN study) statistics

 CASPIAN researched OS data for 3 years

 CASPIAN researched OS data for 3 years, leave a message here