Preface

The traditional treatment methods of tumor include surgical treatment, radiotherapy and chemical drug treatment. All those that treat tumor through chemical drugs are collectively referred to as chemotherapy, as well as the rise of gene therapy and biological therapy in recent years. At present, surgery is still the preferred or main treatment for malignant tumors (solid tumors). Radiotherapy and chemotherapy before and after surgery are called adjuvant therapy. Neoadjuvant chemotherapy refers to systemic chemotherapy before local treatment (such as surgery or radiotherapy). The purpose is to reduce the mass and kill invisible metastatic cells as soon as possible, so as to facilitate subsequent surgery, radiotherapy and other treatment. Immunotherapy has made a lot of research progress in recent years. It has been approved to be applied to multiple cancer species. After chemotherapy and targeted therapy, it has also become one of the adjuvant therapies, and the immunoadjuvant therapy or neoadjuvant therapy of multiple cancer species has been included in the NCCN guidelines.

Colon Cancer NCCN2022.V1

It is recommended that immunotherapy be included in neoadjuvant chemotherapy

In the 2022 V1 version of the NCCN guidelines for colon cancer, COL-2 adds Nivolumab ± Ipilimumab or Pembrolizumab to the previous chemotherapy regimens (FOLFOX and CAPEOX) for the neoadjuvant treatment options that can be considered for T4b patients with dMMR/ MSH-H.

▲ Relevant Guidelines

This guideline update is based on the NICHE study, which included 40 patients with stage I ~ III colon cancer, including 21 patients with dMMR and 20 patients with pMMR (1 patient with both pMMR and dMMR). dMMR group achieved 100% (20 / 20) pathological remission rate, 95% (19 / 20) main pathological remission rate and 60% (12 / 20) PCR rate in a short time, and verified that immunotherapy has the characteristics of lasting curative effect once it benefits. The results show that nivolumab + ipilimumab combined regimen is completely suitable for neoadjuvant immunotherapy in patients with dMMR non metastatic CRC.It is safe, feasible and well tolerated. The incidence of grade 3 ~ 4 immune related adverse events is 13%, and it will not significantly affect the follow-up operation, and there will be no unexpected and redundant complications after operation.

Non-small cell lung cancer: opdivo + chemotherapy combined with neoadjuvant chemotherapy has been approved by FDA

On March 5, 2022, the FDA approved the combination of heavy PD-1 inhibitor Opdivo (nivolumab) and platinum containing dual drug chemotherapy as a neoadjuvant therapy for patients with resectable non-small cell lung cancer (NSCLC), regardless of the expression of PD-L1.The press release pointed out that this is the first immunotherapy combination approved for the treatment of non-small cell lung cancer before surgery.

It is worth mentioning that earlier this week, Bristol Myers Squibb just announced that the supplementary biological product license application (SBLA) for this indication has obtained the priority review qualification of FDA. In less than a week, this application has been approved by FDA, and the approval speed is amazing. This approval is based on the results of the phase 3 clinical trial checkmate-816.In this trial, opdivo + chemotherapy before surgery reduced the risk of disease progression, recurrence or death by 37% compared with chemotherapy (HR = 0.63, 95% CI: 0.45-0.87, P = 0.0052).The median event free survival was 31.6 months in the opdivo + chemotherapy group and 20.8 months in the chemotherapy group.In addition, 24% of patients in the opdivo + chemotherapy group achieved pathological complete remission, compared with 2.2% in the chemotherapy group (P < 0.0001).

Introduction to neoadjuvant chemotherapy

Neoadjuvant chemotherapy (Neo-adjuvant chemotherapy), also known as preoperative chemotherapy, is a new treatment model developed on the basis of traditional postoperative chemotherapy. It is applied to many breast cancer, gastric cancer and colorectal cancer. Compared with routine postoperative adjuvant chemotherapy, such as large tumor, the tumor can be reduced by chemotherapy, and the chance of master surgery can be improved. Neoadjuvant chemotherapy can reduce the risk of tumor recurrence. Some researchers believe that tumor cells will become inactive after surgery, and preoperative chemotherapy can directly kill active tumor cells. Preoperative chemotherapy, if the tumor shrinks, it indicates that the tumor is effective for this drug, which can be used as postoperative adjuvant chemotherapy to avoid ineffective treatment due to wrong drug use after operation, so as to evaluate the drug sensitivity of the tumor.

However, for different types of cancer, the corresponding indications of neoadjuvant chemotherapy, the selection of chemotherapy drugs and the customization of chemotherapy regimen cycle are different. Whether it is suitable for neoadjuvant chemotherapy should be evaluated based on the diagnosis and treatment guidelines of each cancer.

Take breast cancer as an example, the definition of neoadjuvant chemotherapy for breast cancer means that systemic chemotherapy for patients with breast cancer who did not find distant metastases before treatment or after local treatment such as surgery or radiotherapy, in 1970s, neoadjuvant chemotherapy was first applied to locally advanced breast adenocarcinoma. Neoadjuvant chemotherapy for breast cancer has gradually formed anthracycline and taxane based chemotherapy regimens. Neoadjuvant chemotherapy has become an important part of systemic therapy for breast cancer. Neoadjuvant chemotherapy for breast cancer is a clear goal, which is to improve the rate of resectable surgery and enable breast conserving patients to master breast conserving surgery.

People suitable for neoadjuvant chemotherapy: The suggestions given by CSCO BC (Chinese society of Clinical Oncology) are: ① large lump (> 125px);② Axillary lymph node metastasis;③ HER-2 positive;④ Triple negative;⑤ Those who are willing to preserve the breast, but have a large proportion of tumor size and breast volume, and it is difficult to preserve the breast.

Efficacy monitoring of neoadjuvant chemotherapy: It is necessary to continuously observe the changes of lesions in the process of neoadjuvant chemotherapy. At present, the commonly used methods include physical examination, breast ultrasound, breast molybdenum target, breast magnetic resonance examination and tumor markers.

Neoadjuvant chemotherapy course and scheme:The recommended cycle of neoadjuvant therapy should include at least 6 courses. When neoadjuvant therapy is effective, the expert group recommends that all courses of the proposed scheme should be completed before operation, and the operation should not be carried out in advance. For patients with poor efficacy during neoadjuvant therapy, standardized early efficacy evaluation is particularly important. It is necessary to find these patients as soon as possible, and then adjust the corresponding treatment strategies. We can re puncture evaluation, change chemotherapy regimen or arrange surgical treatment in time.

Neoadjuvant chemotherapy in the era of precision medicine: In the context of precision medicine, the molecular typing of breast cancer is not only related to the regimen of neoadjuvant chemotherapy, but also determines the sensitivity of different treatment regimens and the prognosis of patients.The CTNeoBC clinical trial points out that the prognosis of breast cancer with different molecular typing is inconsistent and limited. Patients with HER-2 negative Luminal breast cancer had better overall prognosis, while for HER-2 positive and three negative breast cancer patients, the prognosis of pCR patients was significantly better than that of non-pCR patients. Non-pCR patients were often not sensitive to subsequent treatment, so pathological complete remission rate could be one of the prognostic information of these two types of breast cancer.

Summary

Precision medical testing can provide guidance information for clinical practice at all stages of neoadjuvant chemotherapy and assist in the formulation of individualized treatment plans. Before neoadjuvant chemotherapy, precision medical testing can predict the sensitive information of patients to drugs and select the high-sensitivity treatment scheme suitable for the patient.

Reference

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