How should phase I-III NSCLC regulate treatment? Let's take a look at the NCCN Guide!
Written by | Yu Shunren
Source | "Medical Community" public account
Targeted therapy and immunotherapy have become the mainstay of treatment for non-small cell lung cancer (NSCLC), and compared with traditional chemoradiotherapy, targeted therapy and immunotherapy have significantly improved the prognosis of patients with advanced NSCLC. At present, with the deepening of research, how should the treatment of patients with NSCLC with different stages be scientific and standardized? Let's take a look at how the National Comprehensive Cancer Network (NCCN) NSCLC Guideline v6 edition [1] recommends.
Patients with early NSCLC
Surgery is the mainstay of treatment for resectable early NSCLC, and for resectable patients with NSCLC, the NCCN guidelines recommend a combination of surgery-based treatments. As an important model of multidisciplinary comprehensive treatment of lung cancer, postoperative adjuvant therapy is an important part of radical surgical resection, which can further improve the prognosis of patients with early-stage lung cancer, reduce the rate of recurrence and metastasis, and prolong survival.
(1) For patients with stage IA (T1abcN0), the NCCN guidelines recommend the following:
Negative margin (R0), postoperative observation without the need for drug therapy;
Positive margin (R1, R2), resection (preferred) or radiotherapy (subsum 2B evidence) can be performed postoperatively;
(2) For patients in IB(T2aN0)-IIA (T2bN0) stages, the NCCN guidelines recommend the following:
Negative margin (R0), postoperative observation, postoperative adjuvant chemotherapy and adjuvant osimertinib therapy (positive for EGFR-sensitive mutations) in high-risk patients;
Positive margin (R1, R2), resection (preferred) ± chemotherapy after surgery, or radiotherapy ± chemotherapy (chemotherapy for patients with stage IIA);
(3) For patients with phase IIB (T3N0; T2bN1), the NCCN guidelines recommend the following:
Negative margin (R0), postoperative chemotherapy and adjuvant osimertinib (positive for EGFR-sensitive mutations);
Positive margin incision is divided into two conditions, R1 patients can undergo reoperative resection + chemotherapy or chemoradiotherapy (sequential or synchronous) after surgery, and R2 patients can undergo reoperative resection + chemotherapy or simultaneous chemoradiotherapy after surgery;
(4) For patients with PHASE IIIA (T1-2N2; T3N1)-IIIB (T3N2), the NCCN guidelines recommend the following:
Negative margin (R0), postoperative chemotherapy and adjuvant osimertinib (class 1 evidence), or sequential chemotherapy + radiotherapy (for N2 only);
Positive margin incision is divided into two conditions, R1 patients can undergo chemoradiotherapy after surgery (sequential or synchronized), and R2 patients can undergo synchronous chemoradiotherapy after surgery.
R0 = no residual tumor, R1 = microscopic residual tumor, R2 = gross eye residual tumor
An exploration of targeted adjuvant therapies
Early complete surgical resection of NSCLC is still the key to improving patient survival, but the risk of recurrence and metastasis of lung cancer after radical resection remains, so postoperative adjuvant therapy is an important part of radical surgical resection, and compared with the past few years, the radical postoperative adjuvant therapy strategy for lung cancer now has one more weapon - targeted therapy.
The ADAURA study is a randomized controlled Phase III clinical study that explored the benefits of osimertinib as an adjunctive treatment regimen for patients with stage IB-IIIB (T3N2, AJCC8) EGFR mutation-positive NSCLC who underwent intact tumor resection (R0). The primary median (disease-free survival) of the ADAURA study was significantly beneficial from DFS, with hr values of 0.17 (95% CI 0.11-0.26), P
Patients with locally advanced NSCLC
Clinically, some patients with NSCLC have developed locally advanced stages at the time of initial diagnosis, and some of them are inoperable. Previous treatment options for patients with unresectable stage III NSCLC were platinum-containing dual-drug-based concurrent chemoradiotherapy with median PFS of only about 8 months and a five-year survival rate of approximately 15 percent [3]. In the process of treatment regimen exploration, the addition of induction chemotherapy, the increase of consolidation chemotherapy, and the increase of radiotherapy dose did not improve the survival of patients, and there was a certain gap with the survival of patients with surgical stage IIIA.
In patients with stage III NSCLC (IIIB, IIIC) that cannot be surgically removed, the NCCN guidelines recommend the following:
For patients with NSCLC who are N3 negative (less than 3 metastatic lymph nodes), treat patients with the same IB-IIIA stage;
For patients with NSCLC who are N3 positive (metastatic lymph nodes greater than or equal to 3), treatment with duvalliumab is recommended after radical concurrent chemoradiotherapy (type 1 evidence);
For patients with NSCLC with metastatic lesions, treatment of metastatic lesions is indicated.
Stage III non-resectable NSCLC chemoradiotherapy remains the cornerstone, and the addition of immunity improves the prognosis of patients
The PACIFIC study confirmed that patients who did not progress after stage III unresectable NSCLC radical chemoradiotherapy had a significant survival benefit from consolidation therapy with varyizumab. The 2021 American Society of Clinical Oncology (ASCO) abstract published updated follow-up data[4], with 5-year OS rates of 42.9% and 33.4%, and 5-year progression-free survival (PFS) rates of 33.1% and 19.0%, respectively, compared with placebo. In mainland China, NMPA has officially approved the use of varyivumab for the treatment of unresectable, stage III NSCLC patients who have not progressed to disease after receiving platinum-based chemotherapy with concurrent radiotherapy.
The position of targeted therapy and immunotherapy in advanced NSCLC is unshakable. Compared with patients with advanced NSCLC, patients with early and middle and advanced stages have the hope of surgical resection, and postoperative adjuvant therapy greatly reduces the risk of recurrence in patients, and the addition of postoperative targeted drugs significantly prolongs the patient's DFS. For non-surgically resectable stage III non-resectable NSCLC patients, the combination of radiotherapy and chemotherapy supplemented by immunotherapy also greatly improves the overall survival of patients. It is believed that with the development of more clinical studies and the release of results, there will be more successful reports on the treatment of phase I-III NSCLC, further expanding the beneficiary population and benefiting more lung cancer patients.
Resources:
[1] NCCN NSCLC Guidelines Version 6.
[2] Wu Y, Tsuboi M,He J, et al. EGFR Osimertinib in Resected-Mutated Non-Small-Cell Lung Cancer. NEngl J Med, 2020, 383: 1711-1723.
[3] Yoon SM, Shaikh T, Hallman M, et al. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol. 2017;8:1–20.
[4] David R. Spigel, et al. Five-year survival outcomes with durvalumab after chemoradiotherapy inunresectable stage III NSCLC: An update from the PACIFIC trial. 2021 ASCO, Abstract 8511.
Materials are supported by AstraZeneca and are intended for healthcare professionals only
Approval number: CN-89906 Expiration date: 2022-12-30
Source: Medical community
Editor-in-charge: Zheng Huaju
Proofreader: Zang Hengjia
Plate making: Xue Jiao