Yale Cancer Center team: These strategies are expected to cure non-small cell lung cancer in the next ten years

According to data from the International Agency for Research on Cancer (IARC), lung cancer is the leading cause of cancer deaths

A few days ago, the Yale Cancer Center research team published an opinion article in Nature-Medical, combing through the progress of individualized treatment of NSCLC that may lead the next decade of diagnosis and treatment.

The paper pointed out that there is always a strategy in the treatment of lung cancer: use the most effective therapy in the early and possible cure

The article first reviews the application of adjuvant radiotherapy and chemotherapy

Nowadays, more and more research evidence also shows that the use of targeted therapy and immunotherapy for adjuvant or neoadjuvant therapy has significant benefits

Targeted drugs for adjuvant therapy

For EGFR mutation-positive lung cancer, the value of targeted adjuvant therapy has been supported by a number of studies

The ADJUVANT-CTONG1104 study led by Professor Wu Yilong showed that in patients with completely resected stage II-IIIA (N1-N2) NSCLC, compared with standard adjuvant chemotherapy, adjuvant gefitinib treatment significantly prolonged disease-free survival Although it did not translate into a significant difference in overall survival, the research team pointed out in the paper that targeted adjuvant therapy followed by subsequent targeted therapy is expected to lead to a longer overall survival.

The ADAURA study strongly shows that osimertinib brings significant benefits to patients with EGFR-mutant NSCLC at different stages (IB-IIIA), and it also effectively reduces the risk of local and remote recurrence

Preliminary studies have suggested that due to the more aggressive pathological and genomic characteristics, the KRAS G12C mutation is associated with worse disease-free survival after complete resection of stage I-III NSCLC

Immunotherapy for earlier NSCLC

In the eyes of several scholars at Yale Cancer Center, the most important advancement in early NSCLC management in the past decade is the application of immune checkpoint inhibitors

The results of the PACIFIC trial showed that the addition of PD-L1 inhibitor durvalumab significantly prolonged progression-free survival in locally advanced (stage III), unresectable NSCLC patients without disease progression after concurrent radiotherapy and chemotherapy Period and overall survival period

This year, the IMpower 010 study showed that after surgery and chemotherapy in patients with stage II-IIIA NSCLC, adjuvant therapy with PD-L1 inhibitor atezolizumab significantly improved disease-free survival, further supporting the use of checkpoint inhibitors In early NSCLC

The application of immune checkpoint inhibitors in preoperative treatment also shows initial hope

Different from the tumor tissue that has been removed or eliminated by radiotherapy during adjuvant therapy (thus limiting the acquisition of tumor antigens), the potential advantage of immune checkpoint inhibitors for neoadjuvant therapy is that it can make T cells and B cells complete tumors Antigen library

At present, there are many phase 2 trials that are exploring the use of neoadjuvant immunotherapy for early intervention of NSCLC

The next goal of lung cancer research: cure

The article pointed out that in order to achieve the goal of cure, the field of lung cancer research should further explore various combination therapies

For tumors with high TMB or other biomarkers, explore neoadjuvant immunotherapy combined with chemotherapy combined with surgery and/or radiotherapy; for tumors driven by oncogenes (carrying EGFR, ALK and ROS-1 mutations and relatively low TMB) , To explore new adjuvant/adjuvant targeted therapy
.
For KRAS G12C mutant NSCLC, the combined application of immune checkpoint inhibitors and KRAS-G12C inhibitors may lead to better outcomes in early disease, especially since we have observed selective KRAS-G12C inhibition against first-generation mutations A variety of drug resistance mechanisms are emerging
.

On the other hand, we need to be more precise and detect recurrence early before the imaging examination can detect it:

We need to understand the correlation between indicators such as complete pathological remission, molecular negative (circulating tumor DNA [ctDNA] is not detectable in plasma) and long-term outcomes such as overall survival after neoadjuvant therapy
.
In prospective clinical trials of M0 disease (recurrence with ctDNA detected but no imaging tests), a comprehensive genomic analysis of all samples is essential for identifying molecular features to predict early recurrence
.

At present, about 50% of early-stage NSCLC patients have a survival period of less than 5 years, which means that there is still a lot of room for improvement in the treatment of these patients
.
A variety of targeted therapies and immunotherapy drugs have been used for the treatment of advanced lung cancer, while the options for non-metastatic NSCLC are relatively limited
.
It is expected that as more evidence accumulates, the application of more innovative therapies will shift to the early stage of the disease, allowing patients to win more opportunities for cure in the early stage
.

Note: The original text has been deleted

Reference

[1] Wang, M.
, Herbst, RS & Boshoff, C.
(2021).
Toward personalized treatment approaches for non-small-cell lung cancer.
Nat Med, DOI: https://doi.
org/10.
1038/s41591- 021-01450-2

[2] New advances in treating non-small cell lung cancer.
Retrieved August 13, 2021, from https://medicalxpress.
com/news/2021-08-advances-non-small-cell-lung-cancer.
html

[3] Le Pechoux C, Pourel N, Barlesi F, et al.
, (2020).
LBA3_PR An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: primary end-point analysis of LungART (IFCT-0503, UK NCRI, SAKK) NCT00410683 [abstract].
Ann Oncol, doi:10.
1016/j.
annonc.
2020.
08.
2280

[4] Zhong Wen-Zhao, et al.
, (2020).
Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial.
Journal of Clinical Oncology, DOI: 10.
1200/JCO.
20.
01820

[5] Wu, Y.
L, et al.
(2020).
Osimertinib in resected EGFR-mutated non-small-cell lung cancer.
N Engl J Med, DOI: 10.
1056/NEJMoa2027071

[6] Forde, P.
M, et al.
(2018).
Neoadjuvant PD-1 blockade in resectable lung cancer.
N Engl J Med, DOI: 10.
1056/NEJMoa1716078