2022 CSCO | Professor Zhou Caicun: Filling the gap to help the future, progress in HER2 diagnosis and treatment and new breakthroughs in ADC drugs

The 25th National Congress of Clinical Oncology and the 2022 CSCO Annual Conference were held
in Beijing on November 5.
The conference focuses on the clinical frontier of oncology, invites well-known experts and scholars at home and abroad to make wonderful progress reports or lectures, and strives to comprehensively and accurately reflect new concepts and new trends
in the field of clinical oncology.
During the conference, Yimaitong was honored to invite Professor Zhou Caicun from Shanghai Pulmonary Hospital affiliated to Tongji University to share the diagnosis and treatment status and progress of patients with HER2 mutation and the new breakthrough
of antibody drug conjugate (ADC) in the field of lung cancer.

Expert profiles

Professor Zhou Caicun

• Director of the Oncology Department of Shanghai Pulmonary Hospital affiliated to Tongji University

• Director of the Cancer Institute of Tongji University School of Medicine

• Executive member of Chinese Society of Clinical Oncology

• Chairman of the Non-Small Cell Special Committee of the Chinese Society of Clinical Oncology

• Chairman of the Thoracic Cancer Branch of the Chinese Medical Association

• Board Member of the International Society for the Study of Lung Cancer (IASLC BOD)

• Member of the Standing Committee of the Lung Cancer Professional Committee of the Chinese Anti-Cancer Association

• Vice Chairman of the Clinical Research Committee of Oncology Drugs of the Chinese Anti-Cancer Association

• Member of the Standing Committee of the Oncology Branch of the Chinese Medical Doctor Association

• Vice Chairman of Shanghai Anti-Cancer Association

• Chairman of the Lung Cancer Molecular Targeting and Immunotherapy Committee of Shanghai Anti-Cancer Association

• Vice President of Oncology Branch of Shanghai Medical Doctor Association

• Vice Chairman of Oncology Branch of Shanghai Medical Association

  
  

Progress in the diagnosis and treatment of HER2-mutated non-small cell lung cancer (NSCLC).

Professor Zhou Caicun

Shanghai Pulmonary Hospital Affiliated to Tongji University

Similar to EGFR mutations, HER2 mutations NSCLC are also associated
with non-smoking, lung adenocarcinoma histology type.
Traditionally, clinicians would assume that "innocent" patients had lung cancer because they usually do not smoke
.

For HER2-mutant NSCLC, there are few targeted drugs, and previous studies have shown that apatinib is almost ineffective, while the targeted drug that has the opportunity to be used for HER2-mutant NSCLC is the domestic drug pyrrotinib, and clinical studies have shown that the objective response rate (ORR) of post-line use of pyrrotinib is 30%, and the median progression-free survival (PFS) is 6.
8 months ^[1].

。 Professor Zhou Caicun pointed out that among traditional targeted therapy drugs, the results of this study should be the best at present, which deserves our continued attention
.

The second class of drugs is ADCs, such as the well-known DS-8201, DS-8201 has good clinical performance in the field of HER2 mutation NSCLC treatment, in the treated patients, DS-8201 post-line treatment of HER2 mutation patients ORR is 58%, median PFS is 8.
2 months, which is quite good results ^[2].

。 As early as 2020, DS-8201 received breakthrough therapy designation, and recently, DS-8201 has been approved by the FDA for the treatment of patients with HER2 mutation-treated metastatic NSCLC ^[2].

We also hope that DS-8201 will enter China as soon as possible to benefit Chinese patients with HER2 mutant lung cancer
.

Professor Zhou Caicun pointed out that in general, Chinese doctors' understanding of HER2 mutation patients is not sufficient, and many patients may not routinely detect HER2 mutation
clinically.
Our goal, and the next step we need to do, is to establish a standard diagnostic protocol, which needs to first screen out patients with HER2 mutations so that these patients can use better targeted drugs
.
To this end, in April this year, Chinese experts released an expert consensus on HER2 mutation detection in ESMO Open ^{magazine [3]}, hoping that the release of this expert consensus can help the diagnosis and treatment
of HER2 mutation NSCLC in the future.

Novel ADC combined with immunization targeting TROP2 is expected to advance the treatment status of patients with high expression of PD-L1

Professor Zhou Caicun

Shanghai Pulmonary Hospital Affiliated to Tongji University

The TROPION-Lung02 study explored the efficacy and safety
of Dato-DXd+ pembrolizumab ± platinum-containing chemotherapy (dual or triple-drug) for metastatic NSCLC.

Preliminary data released at this year's WCLC conference showed that in the first-line treatment cohort, the ORR of the two-drug combination and the three-drug combination was 62% and 50%, and the disease control rate (DCR) was 100% and 90%, respectively ^[4].

。 Based on the good results, the investigators are further advancing clinical research and are currently conducting a phase III TROPION-Lung08 study in patients with high PD-L1 expression to explore the efficacy
of Dato-DXd+ pembrolizumab versus pembrolizumab for the first-line treatment of PD-L1 TPS≥50% of patients with metastatic NSCLC.

Professor Zhou Caicun pointed out that this is a key important clinical study
that is likely to succeed.
For patients with PD-L1 high-expression NSCLC, researchers have tried many regimens to further improve the efficacy, such as the combination of immunotherapy and VEGFR anti-angiogenic drugs, but related clinical studies have failed
.
Other studies have shown no statistically significant difference in PFS results between TIGIT monoclonal antibody combined with immunotherapy versus immunomonotherapy, but overall survival (OS) results are still worth looking forward to
.

Professor Zhou Caicun believes that the ADC class new drug targeting TROP2 combined with pembrolizumab is the most likely to surpass immunotherapy monotherapy as a new regimen, Professor Zhou Caicun is full of confidence in the combination of this new drug, hope that the relevant research can be advanced as soon as possible, in a few years, PD-L1 high expression NSCLC patients may have a better program available, hope that the treatment status of these patients can go a step forward, which is what clinicians expect
。

References:

[1] Zhou C, Li X, Wang Q, Gao G,et al.
Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study.
J Clin Oncol.
2020 Aug 20; 38(24):2753-2761.
doi: 10.
1200/JCO.
20.
00297.
Epub 2020 Jul 2.
PMID: 32614698.

[2]

[3] Ren S, Wang J, Ying J, et al.
Consensus for HER2 alterations testing in non-small-cell lung cancer.
ESMO Open.
2022 Feb; 7(1):100395.
doi: 10.
1016/j.
esmoop.
2022.
100395.
Epub 2022 Feb 8.
Erratum in: ESMO Open.
2022 Apr 20; 7(3):100482.
PMID: 35149428; PMCID: PMC8844658

[4] MA13.
07 - TROPION-Lung02: Initial Results for Datopotamab Deruxtecan Plus Pembrolizumab and Platinum Chemotherapy in Advanced NSCLC.
2022 WCLC.