Advancements in Gynecological Cancer Treatments: Targeted Drugs and Immunotherapy

2024-02-20 08:48:16

Author: Cancer Hope Foundation

Image: shutterstock (illustration not party involved)

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Among the top ten cancers in women, endometrial cancer, ovarian cancer and cervical cancer account for three, seriously threatening women’s health. In the past, the most common female cancer in my country was cervical cancer, but now it is endometrial cancer, followed by ovarian cancer.

In addition to surgery, the treatment of advanced gynecological cancer requires chemotherapy or radiotherapy to reduce the risk of recurrence. Fortunately, in addition to chemotherapy and radiotherapy, today, as we have entered the era of precision medicine, there are also targeted drugs and immune drugs, which not only improve the effect of treatment, but also further reduce the risk of future recurrence and improve the chance and time of survival.

Consultation/Professor Zhang Tingzhang, Linkou Chang Geng Professor-level consultant physician

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Organized/Cancer Hope Foundation

Zhang Tingzhang, a professor-level consultant physician at Linkou Chang Gung Memorial Hospital, said that in recent years, the use of cancer target drugs and immunotherapy has established first-level evidence in large-scale, multinational randomized clinical trials; compared with previous standard chemotherapy, plus Targeted drugs and immunotherapy can significantly improve treatment effects. Appropriate treatment strategies can be used according to different tumor molecular types, which not only reduces the risk of recurrence, improves efficacy, but also reduces the side effects of treatment. The combined use of radiotherapy and immunotherapy has also shown significant efficacy in clinical trials of advanced cervical cancer.

A woman in her 50s with late-stage ovarian cancer relapses, no regrets after waiting for targeted drugs

Dr. Zhang Tingzhang shared his early experience in using targeted drugs. There was a woman in her 50s who worked in a vegetable market. In 2008, she went to the hospital for persistent abdominal distension and was found to have an inguinal hernia, so she underwent surgery. During the surgery, she found an abnormality in the peritoneum. Nodules, pathological examination revealed that the nodules were serous cancer tissue.

Later, the woman was transferred to his outpatient clinic for further examination and found that the ovarian cancer had metastasized to the peritoneum, liver and diaphragm surface, as well as a large amount of ascites. The previous inguinal hernia was a secondary change caused by the increased negative pressure caused by ascites. Fortunately, After undergoing surgery to remove all visible tumors and chemotherapy, he recovered quite well and returned to the vegetable market.

Six years later, the woman’s cancer recurred and she underwent surgery and chemotherapy again, although it was effective. But the next year, at the end of 2015, his condition worsened again. At this time, there were multiple liver metastases. Imaging examination found many liver metastases, which looked like honeycombs. The beehives were filled with cancer tissue, and they were no longer resistant to chemotherapy. The situation is not optimistic.

When we were at a loss, we happened to be conducting trials of PARP inhibitors (Poly (ADP-ribose) polymerase inhibitor, PARPi), a drug that targets BRCA gene mutations in ovarian cancer. Although Taiwan did not join, we could still secure the use of compassionate therapy. . Therefore, it was recommended that the woman undergo genetic testing using tumor specimens from previous surgeries, and it was found that there was a pathological BRCA1 gene mutation.

Later, we obtained free targeted drugs for her. Fortunately, after three months of targeted drug treatment, follow-up imaging revealed that the metastatic liver tumor had almost disappeared, and the woman had regained her former glory. However, he unfortunately passed away after 7 or 8 months of treatment. But for her and her family, this is a hard-won time that she cherishes very much. Fortunately, PARP inhibitors have now been included in health insurance reimbursement drugs, and can be used for 2 years for patients with pathological BRCA-mutated advanced ovarian cancer.

BRCA gene mutation is the lucky one, targeted drugs can increase survival time by 40%

In terms of tissue types, the most common type of ovarian cancer is epithelial cell cancer, accounting for about 85%. Among them, “high-grade serous adenocarcinoma” is the most common type, and its malignancy is quite high. It is often in the third stage when it is discovered. 20% of this type of cancer has BRCA gene mutations.

Zhang Tingzhang said that tumors with BRCA gene mutations, including BRCA1 and BRCA2 gene mutations, respond well to chemotherapy. Two years of maintenance treatment with targeted drugs after chemotherapy can reduce the risk of recurrence to 30 to 40%, that is, It is said to reduce the risk of recurrence by more than 60%, and the same effect is seen even for patients who have not achieved complete response to surgery and chemotherapy.

In addition, in tumors without BRCA mutations but with homologous recombination deficiency (HRD) changes, the use of PARP inhibitors can also reduce the risk of recurrence by 50%.

The cause of these HRD cancers without BRCA mutations may be the methylation of the BRCA gene. The methylation of the gene will cause the loss of the function of the gene, or related genes that cooperate with the BRCA gene to perform homologous recombination repair. Mutation or methylation leads to the loss of gene homologous recombination repair function.

POLE gene mutation in endometrial cancer has good prognosis, with survival rate exceeding 90%

The most common endometrial cancer in women, about 75% is early stage. In 1983, Soviet physician Bokhman used his clinical observations to divide endometrial cancer into two types based on tissue type:

●Type 1: It is a common endometrioid cancer, accounting for more than 80%, and the prognosis after treatment is better;

●Type 2: includes serous adenocarcinoma, epithelial carcinosarcoma, clear cell carcinoma, etc., and is highly malignant.

In 2013, the Cancer Genome Atlas Research Network of the United States published a paper in Nature magazine that divided endometrial cancer into four different genotypes. Among them, endometrial cancer with POLE (Polymerase-epsilon) gene mutations has a particularly good prognosis. Depending on the stage, the survival rate of patients after surgery, regardless of whether they receive auxiliary treatment or not, is over 90%. Patients with stage 3 or below can almost recover immediately after surgery and will not relapse. POLE mutations account for approximately 12% of type 1 endometrial cancers and 5% of type 2 cancers.

The other is microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (MMRd). For late-stage patients, chemotherapy combined with immunotherapy can reduce recurrence and recurrence by 60% compared with traditional chemotherapy. Risk of death. This type accounts for 22% of type 1 endometrial cancers.

The other two types are P53 mutations, which are mostly found in type 2 endometrial cancers, and endometrial cancers without the above three mutations, which are called no specific molecular profile types. Accounting for about half of all endometrial cancers, most are type 1 cancers in younger people.

P53 mutations can be diagnosed by immunohistochemical staining commonly used in pathology departments. A small number of tumors with abnormal p53 expression will have POLE or MMRd. The clinical manifestations of these tumors are the same as those of POLE or MMRd but different from those of P53 mutations.

Further reading:

“Every part of the body is on fire.” The 40-year-old famous obstetrics and gynecology doctor Wang Leming’s wife was unable to save her stage 4 ovarian cancer. She stood on the operating table and shed tears.

Cervical cancer caused by non-HPV viruses is very difficult, genetic testing can find a chance

Cervical cancer was the most common form 20 years ago. With the popularization of cervical cancer screening in Taiwan, the incidence rate has dropped to 40% of the level before screening. Cervical cancer can be further divided into human papillomavirus associated (HPV-associated) and HPV-independent cancers.

Although most cervical cancers are human papillomavirus-related, that is, they occur due to long-term infection with high-risk HPV, the most difficult to diagnose and treat is HPV-unrelated cervical cancer.

Cervical cancer caused by non-HPV viruses is a relatively rare type of adenocarcinoma. There are less than 300 people in China every year. The cervical smear cells look the same as normal cells under the microscope. It is difficult to detect early. The site of occurrence is in the uterus. The cervical canal is not easy to find during internal examination.

The clinical manifestations include excessive watery vaginal discharge and hardening of the cervical stroma during internal examination. These are not obvious symptoms, and even cervical slices cannot be diagnosed. It requires an experienced gynecological oncologist to examine from all aspects. diagnosis. Therefore, when diagnosed, some cases are already at an advanced stage and have lymph node metastasis.

This cancer can be treated with surgery in its early stages. It does not respond as well to radiotherapy and chemotherapy as common cancers related to human papillomavirus. In advanced patients, almost all patients will relapse within six months to two years. Immunohistochemistry and extensive genetic testing must be performed during the first treatment to select a feasible treatment option.

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(This article is reprinted with permission from the Cancer Hope Foundation. The original text is published here)

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