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Bevacizumab Therapy - Avastin
Medical Oncology

Bevacizumab Therapy - Avastin

About This Department

 
Medical Oncology

Bevacizumab cuts off the new blood vessels a tumor needs. In some cancers that lengthens life by months, and in one it does not at all.

In the trial that launched it, median survival in metastatic bowel cancer rose from 15.6 to 20.3 months when bevacizumab was added to chemotherapy. With atezolizumab it became the first treatment to beat sorafenib in liver cancer. Glioblastoma was different. A trial of 637 newly diagnosed patients found no survival gain and a worse quality of life. Your situation decides it. Send us your pathology, scans and treatment history, and a medical oncologist will tell you whether bevacizumab belongs in your plan.

20.3 vs 15.6
Months of median survival, bowel cancer, with and without
67% vs 55%
Alive at one year, liver cancer, atezolizumab plus bevacizumab
Every 2 or 3 weeks
A 30 to 90 minute infusion with chemotherapy
Free
Oncologist's review of your file
Free consultation
Bevacizumab in one paragraph
A tumor larger than a few millimeters cannot grow without new blood vessels, and it calls them in with a signal protein called VEGF. Bevacizumab, an antibody, soaks up VEGF, so the new vessels fail to form and the chaotic ones already there become more orderly, which also lets chemotherapy reach the tumor better. Patients receive it as a drip, nearly always with chemotherapy or with an immunotherapy drug, and it comes as Avastin and as several biosimilars that are the same molecule made by other companies.

Europe licenses it for the cancers below, each time in a defined combination.

  • Metastatic bowel cancer, with fluorouracil-based chemotherapy.
  • Advanced non-squamous lung cancer, with platinum chemotherapy, and with erlotinib in EGFR-mutated disease.
  • Ovarian, fallopian tube and peritoneal cancer, with chemotherapy and as maintenance, including with olaparib.
  • Advanced or recurrent cervical cancer, with chemotherapy.
  • Liver cancer that cannot be removed, with atezolizumab.
  • Advanced kidney cancer with interferon. Metastatic breast cancer with paclitaxel or capecitabine, a use that has narrowed as newer drugs arrived.

Recurrent glioblastoma is treated with it in some countries, including Turkey. The European label leaves it out, and the trial further down explains the caution.

Avastin and its biosimilars
Avastin is the original brand. Since 2017 several biosimilars have been approved in Europe and the United States, the same antibody made by other companies and tested against the original. Oncology guidelines treat them as interchangeable, and the choice between them is a matter of price and availability. Throughout this page, bevacizumab means either.

What did the trials find?

Twenty years of trials have given bevacizumab an unusual record. Some cancers live longer with it. Others only wait longer for the next progression, and in a few it adds harm without benefit, which makes the specific trial for the specific cancer the thing to ask before agreeing to it.

Where it lengthened life

The pattern
The survival gains come in months, and they come when bevacizumab is added to an effective partner. Time without progression improves more often than survival does, and the gap between the two is where most of the argument about the drug lies.

Bowel cancer, the first trial

In 813 patients with untreated metastatic bowel cancer, adding bevacizumab to irinotecan, fluorouracil and leucovorin raised median survival from 15.6 to 20.3 months and time without progression from 6.2 to 10.6 months. Severe high blood pressure rose from 2.3 to 11 percent and was easily controlled. That result, published in 2004, made bevacizumab the first drug of its kind to reach patients.

The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
Hurwitz and colleagues, New England Journal of Medicine, 2004

Lung, cervix and liver

Lung cancer

ECOG 4599 randomized 878 patients with advanced non-squamous lung cancer to paclitaxel and carboplatin with or without bevacizumab. Survival reached a median of 12.3 against 10.3 months, and the response rate 35 against 15 percent.

The cost was bleeding. Serious bleeding occurred in 4.4 percent against 0.7 percent, and 15 patients in the bevacizumab group died of treatment, five of them from bleeding in the lung. The trial had already excluded squamous tumors, brain metastases and anyone coughing blood for that reason. Those exclusions remain the rule.

Cervical cancer

GOG 240 randomized 452 women with recurrent, persistent or metastatic cervical cancer to chemotherapy with or without bevacizumab. Survival rose from a median of 13.3 to 17.0 months. Responses rose from 36 to 48 percent.

Harm came with it. Grade 2 or worse high blood pressure affected 25 percent against 2, serious clots 8 against 1, and fistulas, abnormal openings between the bowel or bladder and the vagina, 3 against 0 percent, most of them in women treated with pelvic radiation before.

Liver cancer

IMbrave150 randomized 501 patients with liver cancer that could not be removed to atezolizumab plus bevacizumab or to sorafenib, the standard tablet. One year on, 67.2 percent were alive against 54.6, and time without progression was 6.8 against 4.3 months. Serious side effects were equal in the two groups at 56 percent, with severe high blood pressure in 15.2 percent on the combination.

Because bevacizumab can make varices in the esophagus bleed, the trial required an endoscopy within six months beforehand and treatment of any large varices, and that step is still required before the first dose.

Where it did not lengthen life, newly diagnosed glioblastoma

RTOG 0825 added bevacizumab or placebo to radiotherapy and temozolomide in 637 patients with newly diagnosed glioblastoma. Survival did not move. The medians were 15.7 months with bevacizumab and 16.1 with placebo. Time without progression was longer with bevacizumab, 10.7 against 7.3 months, while over time the bevacizumab group reported more symptoms, a worse quality of life and a greater decline in memory and thinking.

Bevacizumab tightens the leaky vessels of a brain tumor. Scans look better and swelling falls, so it relieves symptoms in recurrent glioblastoma and is used for that purpose. Control of the tumor does not follow, and in first-line treatment it is not recommended.

Ovarian cancer and maintenance

How it is used in ovarian cancer

Bevacizumab is added to carboplatin and paclitaxel after surgery for advanced ovarian cancer and continued alone as maintenance for up to a year, where it lengthens the time before the cancer returns. In tumors with a DNA repair defect, maintenance combines it with olaparib.

It is also used with chemotherapy when ovarian cancer returns within six months of platinum, where it relieves fluid in the abdomen. Women with signs of bowel obstruction are not given it, because of the risk of perforation.

What are the side effects, and how is safety checked?

What is particular to bevacizumab

Chemotherapy side effects barely change with it. Nausea, hair loss and low blood counts stay much as they would be without it. Its own side effects come from the same action that starves the tumor, since healthy blood vessels, kidneys and healing wounds also rely on VEGF.

Blood pressure
Measured before every dose. A rise, the most common effect, is treated with ordinary blood pressure tablets. Treatment continues unless the pressure cannot be controlled.
Urine protein
A dipstick before each dose. Protein in the urine means the kidney filter is affected, and a large amount pauses or stops the drug.
Wounds and surgery
The last dose must fall at least four weeks before a planned operation, and the first dose four weeks after one, with the wound fully healed, because bevacizumab slows healing. Dental extractions and ports are planned around it.

This table scrolls sideways on a narrow screen. Swipe or drag to see every column.

Side effects of bevacizumab in the trials above
Effect Trial With bevacizumab Without
Severe high blood pressure Bowel cancer, 813 patients 11 percent 2.3 percent
Clinically significant bleeding Lung cancer, 878 patients 4.4 percent 0.7 percent
Serious blood clots Cervical cancer, 452 patients 8 percent 1 percent
Fistula Cervical cancer, 452 patients 3 percent 0 percent
Severe high blood pressure Liver cancer, with atezolizumab 15.2 percent Not reported against sorafenib
Bowel perforation, clots, high blood pressure Glioblastoma, 637 patients Modestly increased  
  • Severe abdominal pain, with or without fever or vomiting, which can mean a bowel perforation.
  • Coughing or vomiting blood, black stools, or bleeding that will not stop.
  • A swollen painful leg, sudden breathlessness or chest pain.
  • A severe headache, confusion, fits or loss of vision, which can mean a rare brain swelling linked to high blood pressure.
  • A wound that opens or will not heal.

Each of these needs a hospital the same day, where you should say that you are on bevacizumab, give the date of the last dose, and show the treatment plan, because a surgeon who operates on a perforation needs to know that healing will be slow.

How many days in Istanbul, and what decides the cost?

The chemotherapy schedule sets the length of stay in Istanbul, because bevacizumab rides with it. Every two weeks in bowel cancer, every three in lung, ovarian and cervical cancer, and every three with atezolizumab in liver cancer. The first infusion takes 90 minutes, the second 60 and later ones 30 if the first two go smoothly. A patient starting treatment here needs a week. That covers the consultation, the tests and the first cycle. After it, some stay for further cycles, and others continue at home from a written plan, since the drug and its biosimilars are available in most countries. Liver cancer patients need an endoscopy for varices first, which adds a day.

Fly whenever you like between cycles.

What decides the cost

Weight decides the dose. The label gives 5, 7.5 or 15 milligrams per kilogram depending on the cancer, so a heavier patient receives more and pays more, and because vials come in fixed sizes of 100 and 400 milligrams, the leftover in an opened vial may land on the patient's bill as well, a detail worth raising with any unit that quotes by the milligram. Biosimilars cost markedly less than the original brand. No evidence shows one to be safer or better than the other. Ask which product your quote uses. The partner drug is priced separately, and atezolizumab in liver cancer or chemotherapy in the other cancers can cost as much again. Blood, urine and blood pressure checks before each cycle cost little, scans every two to three months cost more, and an admission for a complication is the unknown that a written quote should price in advance. Hospitals in Istanbul do not publish packages for bevacizumab. A written quote should name the product, the dose in milligrams, the partner drug and the cycle interval.

Your own figure follows the free review of your file.

Language, companions and follow-up at home

One coordinator from the international patients team is assigned from your first message and stays with you through the course. The team works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and arranges interpreting in other languages on request. An invitation letter naming the hospital and the treating oncologist is sent ten days before travel, and the international patients office arranges the airport transfer and the hotel for you and a companion. Rooms for anyone admitted have a companion bed. Halal, vegetarian and diabetic meals are available, a prayer room is on site, and a request for a female doctor is passed to the department and met wherever the rota allows. Back home, the coordinator stays reachable on the same WhatsApp number, the written plan goes to your own oncologist, and blood pressure and urine checks continue before every dose.

Bevacizumab FAQ

How does bevacizumab work?
It binds VEGF, the protein a tumor uses to grow new blood vessels. Without them the tumor cannot enlarge beyond a few millimeters, and chemotherapy reaches it better through the vessels that remain.
Is a biosimilar as good as Avastin?
Biosimilars are the same antibody made by other manufacturers and approved on the same evidence. There is no evidence that the original or a biosimilar is safer or more effective, and biosimilars cost less.
How much does bevacizumab add to survival?
It depends on the cancer. In metastatic bowel cancer median survival rose from 15.6 to 20.3 months, in cervical cancer from 13.3 to 17.0, and in lung cancer from 10.3 to 12.3. In newly diagnosed glioblastoma it did not improve survival.
What are the main side effects?
High blood pressure, protein in the urine, bleeding, blood clots and slower wound healing. Bowel perforation and fistulas are rare and serious. Blood pressure and urine are checked before every dose.
Can I have surgery while on bevacizumab?
Only with a gap. The last dose should be at least four weeks before a planned operation, and the next dose at least four weeks after it, once the wound has healed.
Can I continue the treatment at home?
Yes, in most cases. After the first cycle here, the plan is written for your own oncologist, and the drug is widely available, often as a biosimilar.
First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma.
RTOG 0825, New England Journal of Medicine, 2014

References

  1. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England Journal of Medicine. 2004;350(23):2335-2342.
  2. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New England Journal of Medicine. 2006;355(24):2542-2550.
  3. Tewari KS, Sill MW, Long HJ, et al. Improved survival with bevacizumab in advanced cervical cancer. New England Journal of Medicine. 2014;370(8):734-743.
  4. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. New England Journal of Medicine. 2020;382(20):1894-1905.
  5. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. New England Journal of Medicine. 2014;370(8):699-708.

Editor's note

Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Metin GÜDEN, Radiation Oncology.

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