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Stage 4 Cancer

Metastatic Cancer or Stage 4 Cancer, Stage IV

Metastatic cancer, or stage 4 cancer, is a medical term describing a condition where the tumor that started in a specific organ is detected in another organ or location distant from that source organ, also called the “primary tumor”. For example, breast cancer metastases can be diagnosed in the lungs, brain, bones, and liver.

It is important to note that a metastasis is the same tumor as the original tumor, even if it has settled in another organ, and the treatment is addressed accordingly. For example, treatment for lung cancer that has metastasized to the liver will be determined according to the treatment for metastatic lung cancer, not according to the treatment for liver cancer.

The Process of Metastasis Formation

Cancer cells from the original, primary tumor can be released into the bloodstream and lymphatic system, flow through them to distant organs or those adjacent to the primary tumor, “settle” there, and grow.

There are types of cancer for which it is known where metastases can form, for example:

  • Breast cancer can send metastases to the bones, brain, liver, and lungs.
  • Lung cancer can send metastases to the brain, bones, liver, and kidney.
  • Prostate cancer can send metastases to the bones.
  • Colon and rectal cancer can send metastases to the liver and lungs.
Breast cancer metastasis formation process

Chances of Recovery from Metastatic Cancer, Stage 4

In the vast majority of metastatic cases, treatments are not curative. The therapeutic goals are slowing the tumor growth rate, extending life, reducing disease symptoms, and improving the patient’s quality of life.

The efficacy of treatments is affected by multiple factors, including: cancer type, number and location of metastases, tumor burden in the patient’s body, growth rate of cancerous lesions, the patient’s treatment history, background diseases, the tumor microenvironment among the cancer cells themselves, resistance the cancer has developed to previous treatments, and more.

Innovative Personalized Treatments and Clinical Trials in Metastatic Stage 4 Cancer

For most cancer patients, existing treatments do not cure the cancer, hence the need for innovative and effective strategies to fight the disease.

The National Cancer Institute in the USA, the NCI, recommends that patients with advanced-stage cancer participate in one of the many clinical trials existing worldwide to increase therapeutic success chances. Joining this recommendation is the umbrella organization of leading US cancer centers, the NCCN, emphasizing that every patient should be encouraged to participate in clinical trials at every stage of the disease:

“Patients with cancer should be encouraged to participate in clinical trials during all aspects of their diagnosis and treatment”

Today, every patient will be treated with the standard protocols mentioned above, and sometimes the oncologist will offer to join trials open at their institute.

Advancement in cancer treatments lies in clinical trials, where the most advanced and interesting drugs are found, some of which have even earned FDA recognition as “Breakthrough Therapies,” with more data required from studies until final official approval.

A whole world of trials and compassionate use treatments is open and available globally, and it is important to know which treatments from the forefront of science exist worldwide that the patient can benefit from much more than any conventional treatment offered.

For most patients with malignant cancer, existing treatments do not cure the cancer, hence the need for innovative and effective strategies to fight the disease.

You are invited to read our publications about innovative and breakthrough treatments from around the world for metastatic stage 4 cancer >>


Common Questions about Stage 4 Cancer (Summary)

Q: What is the difference between metastatic cancer and primary cancer?

Metastatic cancer (Stage 4) is a condition where cells from the original tumor have migrated to other organs. Treatment is always determined by the origin of the primary tumor, not the organ where the metastasis was detected.

Q: Are there treatments beyond the standard protocol?

Yes. Beyond the standard protocol, there are clinical trials worldwide, compassionate use drugs, and advanced biological treatments (Off-label) that may suit the specific characteristics of the tumor.

Q: Why does the NCI recommend clinical trials?

Because that is where progress lies. Clinical trials allow access to breakthrough drugs that have not yet reached final approval and may be more effective than existing standard treatment.

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A novel drug gets Breakthrough Designation in combination with Opdivo® in Melanoma

Background

Bempegaldesleukin, NKTR-214, and nivolumab, Opdivo, was granted breakthrough deisgnation by the FDA for the first line treatment of patients with previously untreated unresectable or metastatic melanoma.

Bempegaldesleukin, NKTR-214, is a substance designed to stimulate the patient’s own immune system to fight cancer.

In melanoma, Opdivo is FDA approved as a single agent for the treatment of patients with unresectable or metastatic disease, and also in combination with Ipilimumab, Yervoy, for the treatment of patients with unresectable or metastatic disease.

53% of Melanoma patients responded to the combination of NKTR-214 and Opdivo and 34% reached a complete remission of the disease. This ongoing phase I/II PIVOT-02 trial is the basis for the FDA deisgination.

What is breakthrough designation?

When preliminary clinical trials indicate that a therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases, the FDA grants the therapy a breakthrough designation. This designation allows the FDA to expedite the review process and if the FDA is convinced about the data and results of the clinical trials, the therapy is approved and become available to patients in a much shorter time.

About PIVOT-02 trial

In the multicenter PIVOT-02 trial, there was a range of solid tumors. In the melanoma cohort, 41 patients were enrolled and received ≥1 dose of NKTR-214/Opdivo. As of the data cutoff date, which was March 29, 2019, 38 patients were evaluable for efficacy; 3 patients had discontinued prior to the first scan due to an unrelated treatment adverse event and patient decision.

Trial findings

Interim findings were presented at the ASCO Annual Meeting 2019 two months ago and showed that 53% of Melanoma patients responded to the combination of NKTR-214 and Opdivo and 34% reached a complete remission of the disease.

The disease control rate, which is the total percentage of Melanoma patients who responded to the combination including minor response and stable disease, was 74%.

In PD-L1–positive, PD-L1–negative, and PD-L1–unknown tumors, the responses were 62%, 43%, and 33%, respectively.

There was a 100% reduction in target lesions in 42% of patients.

Overall, responses were observed regardless of PD-L1 expression or unfavorable tumor microenvironments.

Regarding safety

All of the severe treatment-related adverse events were reported in 6 patients and included atrial fibrillation; hyperglycemia; and acute kidney injury, blood creatinine increase, dyspnea, hypernatremia, and hypoxia.

The future

The ongoing phase III PIVOT 1O 001 trial is evaluating NKTR-214in combination with Opdivo versus Opdivo alone as frontline therapy for patients with advanced melanoma.

To conclude

The best treatment for a cancer patient is to get the most advanced cancer drugs in advanced stages of development. There, the hope and the chance to extend life go far beyond the standard protocols.

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Improving therapeutic success, extending life and quality of life are our main business. We extend to metastatic cancer patients and patients with brain tumors, the most advanced treatment options in the world and the best experts in Israel and abroad.

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