AVASTIN (Bevacizumab)-Info for Danny-Personal stories-Clinical reports-Advantages vs. Disadvantages-

LorettaMarshall
LorettaMarshall Member Posts: 662 Member
in Ovarian Cancer #1

Dear Danny:

Looks like you and your wife are still experiencing what many of us on this link are engaged in as well, an ongoing fight with cancer bombarding our body.    We all understand your anguish and frustration.  From the dates you gave us, it looks like your wife has “seemingly” been in remission for a little over 2 years.  I say “seemingly” because we cancer patients can be “seemingly” doing just fine, and don’t experience anything too different in the way of symptoms but we go for our usual checkups.  Now, of course, while as a Stage IV Peritoneal Carcinomatosis/Ovarian Cancer patient, there will always be progression, I hope it will be minimal. 

My last of series of chemo treatments (6 in a series @/3 week interval) ended in January 19, 2017.  This past January, my medi-port became infected and I had to have it removed. I had it for over 4 years.  So I actually had only 5 treatments this last time.  However, after that, in 4 months’ time, the CA125 count began to increase by double digits.  For instance on February of 2017 it was 23, now in August of 2017 it is 183.  My numbers have never run in the thousands.  My highest number was in the mid-300s.  So we know something is amiss when our numbers rise consistently month after month.  One rise might be a “fluke” but a consistent rise is cause for concern for sure.

My oncologist explained that although the Carbo/Paclitaxel (Taxol) had worked well for me in the past, it appears that it is no longer having the same effect.  He said, “We like to see the numbers stable for at least 6 months following any treatment regimen.  He seems to feel that this particular combo is “wearing out its welcome” in my body. (My words)  And when clinical trials are given, they expect to see a marked improvement in any new drug of at least 6 months duration. 

Avastin has not been proven to help Esophageal or Colorectal patients according to links that I have read, but today you’re interested to know of other’s familiarity with Avastin.  The links that I have referenced are quite long, so I suggest you connect to the link and read the entire article.  In some instances, I’ve only chosen excerpts that caught my attention.  As I say in this letter, to me the deleterious effects of Avastin OUTWEIGH the potential benefits of possibly surviving a mere 3 months longer.  I speak as a Stage IV cancer patient, and know the effects I have already suffered through, and I’m not about to “try one more” for only 3 more months of survival, which would not be absent side effects which are many, during that time.  I speak only for myself, but my mind is made up!   

My oncologist suggested perhaps DOXIL or a clinical trial.  He gives me all the possible options, but I’m the one that makes the final decision.  Since I’ve been reading here about Doxil, I’m not enthused about that treatment.  And of course, the chemo regimen that has worked well for the “greatest” number of OC patients in trials has been Carbo/Taxol.  That is why they are the ones usually prescribed first.  From there, the next drugs that one might choose from are “lower down on the rung of the ladder.  However, that doesn’t mean that it won’t work for some.  But at this stage, I’m not leaning toward using that drug.  And I’m certainly not using AVASTIN.  Since it’s a gamble at best, I want to look at some of the results of clinical trials going on.  That’s just what they are—trials. 

I’ve signed up for multiple medical alerts relative mainly to Peritoneal Carcinomatosis, which incidentally is not limited to Ovarian Cancer patients.  That condition can arise from more than one organ in the peritoneum.  The other two cancers I mainly follow are Ovarian Cancer and Esophageal Cancer, since my husband is an EC survivor, now entering his 15th year of survival.  That’s a deadly cancer, and most do not survive it.  We thank God every day for continued survival.  I’ve been a Stage IV cancer patient since November of 2012.  You can read more “about me” by clicking on the picture of my husband William and me if you wish.

As for your remarks about surgeons opening the abdomen and closing it back up without removing the “3 cm X 3cm collection”, (3 centimeters is 1.1811 inches), I’m not familiar with the word “collection”.  I’m guessing it is a “mass” in one place that carries with it that 3 cm measurement.  I was diagnosed with Peritoneal Carcinomatosis first here at my local emergency room.  A CT scan was done, and multiple tumors were found “floating around in the peritoneal fluid in my abdomen.”  Then I went for a SECOND OPINION at the University of Pittsburgh Medical Center (UPMC).  There exploratory surgery and a PET scan revealed cancer in both ovaries as well.  My PC diagnosis was terminal even before I learned that the ovaries were cancerous.  So most likely my primary cancer was in the ovaries all along, and then it metastasized to the abdomen.  In any event, Carbo/Paclitaxel (Taxol) is the treatment recommended for both PC and OC.

However, your specific question is about whether or not you and your wife should agree to Avastin (bevacizumab).   Ever since I had a letter from “Carole” years back now about the deadly effect AVASTIN had on her husband who had been diagnosed with Esophageal Cancer, I kept that letter in my files.  That had a tragic ending.  So I’ve already told my oncologist, I will NOT ever agree to Avastin.  And since then, I have kept up with medical reports on Avastin.  So below are some of my files relative to this drug.  You can make your own decision.  I will include the letters from Carole as well as a letter from a lady who posts here right now.  She goes by the name of “Guitardiva”.  The combination of Doxil and Avastin have been so debilitating and with so many deleterious side effects that she is not going to continue to take that combo.  I don’t blame her.  

You haven’t mentioned whether or not you two have gone for a SECOND opinion, but I would highly recommend it since many first opinions are wrong.  And if you’re dealing with the same doctors that you started with, it would be to your advantage to get a second opinion, since obviously the CA125 count could well indicate a progression or metastasis of this Stage III OC cancer.  It may be that another surgeon might want to consider “Cytoreductive Surgery” or even a HIPEC treatment.  I won’t go into detail about that here, but it is a surgery that removes (in my case) all “non-essential” organs to which the cancer can further spread.  The “HIPEC- heated intraperitoneal chemo treatment” is sometimes administered as part of the surgery.  So that is something that might be discussed if you seek another opinion.  Obviously this group has not mentioned HIPEC.

When seeking a 2nd opinion, I do hope that you will consult with a major medical center where this HIPEC treatment is part of their practice.  I had my Cytoreductive Surgery at UPMC on July 1, 2013.  The procedure was explained to me prior to surgery, and told that it might be a possibility.  But that determination would not be made until the actual surgery was performed.  My surgeon did not elect to include that.  I wish he had, but I had to trust his judgment and it’s difficult for me to “talk in my sleep!”  So when I awoke, I realized that this was not a part of my experience.  So it is decided on an individual basis and relates also to the number and size of tumors inside the abdominal cavity, and how many were able to be removed.  I’m happy to have survived the surgery, but for the first week or so, I began to wonder whether or not I would survive.  But by the grace of God, I’m still here. 

But remember, I’m not diagnosing your wife.  However, I suggest you do some research on your own before “just taking the doctors’ opinions” as to what would work best.  After all, it’s our body, our life and we only have one life!

You are wise to seek the opinions of others who have similar diagnoses.  There is much to be learned from other Ovarian cancer patients.  We’re sorry to have to meet under these circumstances.  This is a big problem for a young woman now only 33 years of age.  If I were you, I would have a long list of questions for your wife’s doctors.  Perhaps you will need another physician’s recommendations if all this group can suggest is AVASTIN.  That is what I would do “if I were in your shoes.”  And so I wish for the two of you the best possible outcome in the days going forward.  I hope that some of the information you will read below will give you a better understanding of treatments for Ovarian Cancer. 

Most sincerely, Loretta

P.S.  I’ve included several reports about Avastin, and put them in chronological order.  It seems the high hopes for another type of treatment AVASTIN has not really happened the way I interpret these reports.  So here is a variety of information you may find helpful.  Be forewarned, it is voluminous and will take some time to read, but I think you will have made a decision by the time you look into the advantages vs. disadvantages of adding AVASTIN (bevacizumab) to any treatment recommended in the future.

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1.      http://www.gomn.com/news/mayo-clinic-says-get-a-second-opinion-first-ones-are-frequently-wrong/

“Mayo Clinic says get a second opinion – first ones are frequently wrong

by Melissa Turtinen - April 4, 2017 12:17 pm

If you’re diagnosed with an illness, you might want to get a second opinion.

The Mayo Clinic in Rochester did a study (published in a medical journal Tuesday) and found as many as 88 percent of patients who came to the clinic for a second opinion for a complex condition left with a new or more refined diagnosis, a news release says.

The Mayo Clinic says a different or more detailed diagnosis can change someone’s care plan “and potentially their lives…”

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2.      https://www.reference.com/science/3-centimeters-look-like-88ce0ea961592fb9

Q:What does 3 centimeters look like?

“To visualize 3 centimeters, think about the end of the average thumb. From the first joint to the tip is approximately 1 inch. Three centimeters is approximately 1 3/16 inches, so 3 centimeters is just slightly longer than the average thumb from the first knuckle to the tip.  Each inch equals 2.54 centimeters. Three centimeters is about half a centimeter longer than 1 inch. On a standard ruler, find 1 inch and add 3/16 of an inch for an estimate of 3 centimeters. Other visual representations of approximately 3 centimeters include a dollar bill folded in half lengthwise, for a measure of about 3.2 centimeters, or a the diameter of a quarter, which is 2.5 centimeters across.”

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Doxil/Avastin after recurrence – Several remarks from Guitardiva who hasn’t posted since July 19, 2017.  I imagine she is still feeling poorly. 

 3.      https://csn.cancer.org/comment/1583381#comment-1583381

Guitardiva’s remarks about no quality of life and she thinks it is the Avastin.

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4.      https://csn.cancer.org/comment/1589259#comment-1589259

Several remarks by “Guitardiva” on this particular topic line relative to Avastin.

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5.      https://csn.cancer.org/comment/1589262#comment-1589262

This is “Guitardiva’s letter of July 19, 2017”.  I mentioned her in my remarks above.

“I have had severe blistering

I have had severe blistering on my hands from the Doxil.  I also developed pancreatitis, likely from the Avastin.  I have also had crushing fatigue, no appetite, losing too much weight, skin like tissue paper, nosebleeds, mouth sores, and a case of diverticulitis.  The carboplatin/Taxol was a picnic compared to this stuff.

Needless to say, I have stopped those drugs.  There didn't seem to be any response (tumors are continuing to pop up in my lymph nodes and now on the liver) and my quality of life the last eight weeks has been abysmal.  Not the protocol for me.  Although it seems like many people tolerate it just fine; my oncologist was quite surprised at all the problems I have been having.”

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6.      https://csn.cancer.org/comment/1016848#comment-1016848  

Here one letter March 7, 2011, that “Carole” wrote as (3Mana) on the Esophageal cancer site, telling about the death of her husband.

“Thinking of you

Grandma Jo,
I'm so sorry that you're going through this with your daughter. It has to be so very hard to watch your child suffer. I hope you cherish every day you have with her. You sound like a great mother. Cancer is such a horrible disease and it can change your life overnight.

I lost my husband of 46 years last March 25th. I can hardly believe it's almost a year since I held him in my arms.

He had been diagnosed in January with lung cancer & lesions in his brain & spine. He had 2 weeks of radiation to his brain & spine which showed good results. Then he had his first chemo treatment with 3 chemos one of which was Avastin.

 He started coughing up blood before his next treatment, so they did a CT scan and said things looked good, but his next chemo would be minus the Avastin. Well it was too late. The damage from Avastin had already been done and he hemorrhaged in the bathroom one night. It was traumatic & I couldn't do anything except call 911. They worked on him for 45 min. but it was too late. I question the Avastin because on the info it said "can be a RARE side effect--hemorrhaging. Since it did say rare, guess we had faith that it wouldn't happen. But it did!
Sorry I'm rambling. Please be strong and give your daughter a hug for me, okay?
Friends, Carole”

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7.      https://csn.cancer.org/node/206203

Another letter Carole wrote on this link re Avastin

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HIPEC may be something that might be well to discuss if the diagnosis is changing.  My posting here:

8.       https://csn.cancer.org/node/309344 has some good information and videos relative to HIPEC.

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9.      http://www.internalmedicinenews.com/index.php?id=2049&type=98&tx_ttnews[tt_news]=60465&cHash=da03e20e36

[My note:  Unfortunately this link is no longer available on the web but I have it copied in my file. (www.InternalMedicineNews.com) so I will print it here.  The gist of the article says that while Avastin has not been withdrawn completely as a treatment for some other types of cancers, it has not shown to be an improvement for those BC patients that have taken it.  When considering the use of new drugs in a clinical trial, there is an “end point” and obviously for breast cancer patients, this drug did not prolong the “progression free survival” time over other drugs already approved.  Note this statement in the article below.  Another link relative to Ovarian Cancer patients is included in my list of references as well. And I’m not impressed with a few short months of progression free survival as opposed to the many toxic side effects of this drug Avastin.  LM]

Here is the article that I kept in my files.  “Panel Backs FDA Pulling Plug on Avastin

By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network- 06/29/11

SILVER SPRING, MD. – In a series of three unanimous votes, a Food and Drug Administration advisory panel supported the agency’s decision to withdraw approval of BEVACIZUMAB FOR METASTATIC BREAST CANCER.

Panelists voted 6-0 on June 29 that the available evidence does not show bevacizumab (Avastin) to be safe or effective for the first-line treatment of women with metastatic HER2-negative breast cancer, in combination with paclitaxel.

Their decision came at the conclusion of an unprecedented 2-day hearing requested by bevacizumab manufacturer Genentech Inc., a subsidiary of Roche, which appealed the FDA’s proposal in December 2010 to withdraw the accelerated approval of the antiangiogenesis agent for this indication.

The proposed withdrawal is based on subsequent studies failing to confirm a benefit in progression-free survival that was associated with the treatment in an open-label, multicenter, randomized trial. In addition, serious treatment-related adverse events, including deaths, led the FDA to conclude that bevacizumab has an unfavorable risk-benefit profile for this indication.

“In the absence of clinical benefit, I don’t think any toxicity is acceptable,” said one of the panel members, Dr. Wyndham Wilson, chief of the lymphoma therapeutics section, in the Center for Cancer Research at the National Cancer Institute, Bethesda, Md.

Along with other panelists, he contended that the studies did not show any clinically meaningful improvements in progression-free or overall survival. In another 6-0 vote, the panel agreed that the two subsequent studies – the AVADO and RIBBON1 trials – failed to verify the benefit for the breast cancer indication that was seen in the earlier study.

And the panel voted 6-0 that the FDA should not continue the approval of the breast cancer indication, while the sponsor designs and conducts additional studies intended to verify the drug’s clinical benefit.

With these votes, the panel of outside experts from the Oncologic Drugs Advisory Committee – a group that included a biostatistician, a patient representative and four oncologists – agreed with the FDA’s grounds for recommending that the drug be withdrawn for this indication.

Subsequent to the hearing, the FDA announced that it will take comments until July 28. The final decision will be made by FDA Commissioner Dr. Margaret Hamburg after that date.

Because BEVACIZUMAB is approved for kidney, colon, brain, and lung cancer, the decision will not affect its availability on the market, BUT INSURANCE COVERAGE FOR THE COSTLY TREATMENT WOULD BE UNLIKELY.

The FDA based its accelerated approval on the E2100 study, which found that median progression-free survival (PFS), the primary end point, was 5.5 months longer among the women treated with a combination of BEVACIZUMAB and paclitaxel (TAXOL) than among those treated with PACLITAXEL ALONE, which was significant.

But in the AVADO study, median progression-free survival was less than a month longer among the patients in the two bevacizumab plus docetaxel arms, compared with those on docetaxel alone. In RIBBON1, the median was 1.2 months longer when taxane/anthracycline was added to bevacizumab.

NONE OF THE STUDIES FOUND A BENEFIT IN OVERALL SURVIVAL, the gold standard. NOR DID THEY SHOW IMPROVEMENT IN QUALITY OF LIFE.   IN ADDITION BEVACIZUMAB WAS ASSOCIATED WITH SERIOUS ADVERSE EVENTS.

At the hearing, Genentech maintained that the E2100 study was a well-conducted “highly influential” study that had robust results, and was not invalidated by the two follow-up studies, which met their primary end points for progression-free survival, with differences that carried statistically significant P values.

The company said that no new safety signals were seen in the studies, that the drug’s adverse event profile is well-known, and that effects like proteinuria and hypertension are generally manageable. It contended that bevacizumab combined with paclitaxel had a favorable risk-benefit profile as a first-line treatment of metastatic breast cancer –and that its safety profile was in line with other first-line metastatic breast cancer treatments.

The company also said that access to the treatment should be maintained for women with triple-negative metastatic breast cancer, as they have few treatment options.

But FDA officials explained that based on the overall data, the agency decided that the BENEFITS DO NOT OUTWEIGH SERIOUS AND POTENTIALLY LIFE-THREATENING RISKS, which can include INTESTINAL PERFORATIONS, IMPAIRED WOUND HEALING, AND HEMORRHAGES.

Bevacizumab, an antiangiogenic agent marketed as AVASTIN, binds to vascular endothelial growth factor (VEGF), thereby working to cut off blood flow to tumors.  It is approved in 84 countries as a first-line treatment of metastatic breast cancer, and approval in combination with PACLITAXEL was retained by the European Medicines Agency earlier this year.

Genentech officials argued that bevacizumab fulfills an unmet need for treatments for this population of patients. In the last 30 years, they noted, gemcitabine plus paclitaxel has been the only other non-hormonal regimen approved in the United States as a first-line treatment of HER2-negative or HER2 unspecified metastatic breast cancer.

The company issued a statement after the meeting expressing its disappointment and avowing that it remains “ready to collaborate with the FDA to find a solution that is in the best interest of patients who need Avastin.”


FDA Approves Avastin to Treat Ovarian Cancer

The FDA approves Avastin in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer, based on results of the phase 3 AURELIA trial.

SILAS INMAN @silasinman - PUBLISHED: NOVEMBER 14, 2014

 Discussions >>  Talk about this article with other patients, caregivers, and advocates in the Ovarian Cancer CURE discussion group.

The Food and Drug Administration (FDA) has approved Avastin (bevacizumab) in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer, based on a 62 percent improvement in progression-free survival (PFS) experienced by patients treated with the VEGF inhibitor in the phase 3 AURELIA trial.

The approval follows a priority review, which the FDA reserves for therapies that demonstrate a significant improvement over standard options. In the AURELIA study, the median PFS with Avastin was 6.8 compared with 3.4 months with chemotherapy alone. The objective response rate was 28 percent versus 13 percent, and the median overall survival was 16.6 compared with 13.3 months, with Avastin and chemotherapy, respectively…

The addition of Avastin to chemotherapy resulted in an increase of grade 3/4 hypertension and hand-foot syndrome.

Gastrointestinal perforation was seen in 2 percent of patients treated with Avastin compared with none treated with chemotherapy alone.

Results from the AURELIA trial add to several prior phase 3 trials that demonstrated Avastin effectively extends PFS for women with ovarian cancer. In the GOG-0218 and ICON7 studies, Avastin extended PFS for women with advanced ovarian cancer that had not been previously treated. In the OCEANS trial, Avastin improved PFS in women with recurrent, platinum-sensitive disease. However, across the multiple large trials, an extension in survival was not demonstrated…”

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11.  http://www.medpagetoday.com/MeetingCoverage/SGO/50720?xid=nl_mpt_DHE_2015-03-31&eun=g67937d0r&userid=67937&mu_id=5067363

Meeting Coverage  03.30.2015 - “MIXED RESULTS FOR AVASTIN PLUS CHEMO IN OVARIAN CANCER

Regimen improves survival but study misses cutoff for statistical significance…

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Note that this randomized trial of carboplatin-paclitaxel with or without bevacizumab demonstrated no significant difference in overall survival between the arms, but the strong trend towards bevacizumab benefit has led some to argue that practice should change.
  • Be aware that adverse events occurred more frequently in the bevacizumab-treated arm.

CHICAGO -- Women with recurrent, platinum-sensitive ovarian cancer obtained an unprecedented survival benefit with a chemotherapy-bevacizumab (Avastin) combination, but the improvement still failed to achieve statistical significance.

Patients who received carboplatin, paclitaxel, and bevacizumab had a median overall survival (OS) of 42.2 months compared with 37.3 months for platinum-taxane doublet. Nonetheless, the 5-month difference just missed the trial's cutoff for statistical significance (P=0.056 versus P=0.05).

Bevacizumab-treated patients did have a statistically significant improvement in progression-free survival (PFS), a secondary endpoint, as reported here at the Society of Gynecologic Oncology meeting…

The findings and discussion revolved around the Gynecologic Oncology Group (GOG) 213 study, a randomized, phase III trial involving patients with platinum-sensitive recurrent ovarian cancer (defined as complete response to platinum-based first-line chemotherapy and PFS of at least 6 months).

The trial had two objectives: evaluate the potential benefits of secondary cytoreductive surgery following recurrence and compare standard chemotherapy along or in combination with bevacizumab…

Adverse events occurred more frequently with bevacizumab, including grade 3-plus thromboembolism (4% versus 1%),

infection (13% versus 6%),

hypertension (12% versus 1%),

and proteinuria (8% versus 0%).

 Gastrointestinal perforation, fistula, or abscess (all grades) also occurred more often in the bevacizumab arm (15% versus 4%)…

  • The GOG213 trial was supported by the National Cancer Institute… Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine
  • Primary Source - Society of Gynecologic Oncology…”
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12.  http://www.medpagetoday.com/clinical-context/GynecologicCancers/56872

cme/ce Clinical Context 03.22.2016 - “SGO: Optimal Chemo for Ovarian Cancer Fails to Emerge

No PFS difference among three regimens evaluated in key trial

  • by Charles Bankhead - Staff Writer, MedPage Today

Action Points

  • Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Results of a long-awaited ovarian cancer trial failed to show an advantage for any of three chemotherapy regimens.
  • Note that the regimens -- involving combinations of intraperitoneal (IP) and intravenous (IV) chemotherapy plus bevacizumab (Avastin) -- led to a median progression-free survival of 27 to 29 months in patients with optimally debulked stage II-III disease.

SAN DIEGO -- A roomful of gynecologic oncologists walked away disappointed after results of a long-awaited ovarian cancer trial failed to show an advantage for any of three chemotherapy regimens.

The regimens -- involving combinations of intraperitoneal (IP) and intravenous (IV) chemotherapy plus bevacizumab (Avastin) -- led to a median progression-free survival (PFS) of 27 to 29 months in patients with optimally debulked stage II-III disease.

An analysis limited to patients with optimal stage III disease yielded median PFS values of 31 to 34 months.

The results were a far cry from the 60-month median PFS in optimally debulked patients achieved with a higher dose of IP cisplatin in the Gynecologic Oncology Group (GOG) 172 trial reported more than a decade ago, and the three regimens' median PFS values remained similar to the 24-month median for all patients in GOG 172.

Moreover, toxicity remained a problem, although not nearly as severe as what was observed in GOG 172, reported Joan L. Walker, MD, of Oklahoma University's Stephenson Cancer Center in Oklahoma City, here at the Society of Gynecologic Oncology meeting.

Asked whether it might be time to move on from IP, Walker demurred.

"I honestly believe there is an uncertainty as to what is benefiting the patients in GOG 172. One of those options is that it allows the patient to have a more intense post-recurrence treatment. Carboplatin burns bone marrow and cisplatin doesn't do as bad a job of that. It's possible that patients actually survive longer after IP cisplatin because they have more tolerance to future chemotherapy," she said.

"There also is a possibility of there being an immune response to intraperitoneal chemotherapy, and if there is an immune response the patient might not die as fast. I think the [60-month median] survival in GOG 172 was incredibly provocative, and I don't know what this [current] study will show in terms of survival," she added.

Invited discussant Gini Fleming, MD, of the University of Chicago, had a less-sanguine take on the trial's implications.

"In the current situation, with regard to what is being prioritized in trials, to go back and develop a new IP regimen to test, just isn't going to happen," Fleming said.

"In my mind, we don't have the evidence to continue doing what we're doing, unless we see some very positive data from the ongoing trials."

Michael Bookman, MD, of Arizona Oncology in Scottsdale, might have captured much of the audience's sentiment with a preface to his comments.

"I still have a drink ticket left from last night. Does anyone know how I can use it? Because I think I'm going to need [a drink]."

In a more serious vein, Bookman added, "Taking a look at where we are today, with better supportive care, perhaps better intravenous therapy, I think we really do have to debate what's the path forward.

"We have a lot of interesting targeted agents, immunologic strategies, synthetic lethality, and other things we could be working on," he noted.

"If we have to study IV and IP chemotherapy and really flesh all of that out, it's going to slow us down, we're going to knock out financial resources to do those trials.

It's an important question on behalf of our patients, and on behalf of the research investigators, to understand how we should move forward."

Trial Results

Walker reported findings from the GOG 252, the latest attempt to capture the unprecedented survival benefit observed in GOG 172 while sparing patients the toxicity associated with high-dose cisplatin: Only 42% of patients randomized to IP cisplatin 100 mg/m2 plus IV paclitaxel completed six cycles of therapy.

Results of the GOG 218 evaluation of bevacizumab further complicated efforts to replicate GOG 172 efficacy with less toxicity.

GOG 218 showed a significant improvement in PFS with the angiogenesis inhibitor among patients with advanced ovarian cancer.

GOG 252 involved women with stage II-III epithelial carcinoma of the ovary, fallopian tube, or peritoneal cavity. All patients underwent optimal surgical debulking to 1 cm or less residual disease by surgeon report. Patients were then randomized to one of three chemotherapy regimens:

  • Dose-dense IV paclitaxel, IV carboplatin, and bevacizumab (reference arm)
  • Dose-dense IV paclitaxel, IP carboplatin, and bevacizumab
  • Standard IV paclitaxel followed by reduced-dose IP paclitaxel, IP cisplatin, and bevacizumab

The primary endpoint was PFS. Data analysis comprised 1,560 patients, who had a median age of 58. Patients with stage III disease accounted for 84% of the study population, and 72% of patients had grade 3 serous ovarian cancer. Walker said 57% of the patients had no visible residual disease by surgeon report; however, she expressed doubt that the complete-resection rate would hold up when results of CT assessments become available.

In both of the carboplatin-containing arms, 90% of patients completed at least six cycles of platinum therapy compared with 84% of patients randomized to the cisplatin-containing regimen. In all three arms 87% to 88% of patients completed at least six cycles of taxane administration.

The results showed a median PFS of 26.8 months for patients with optimal stage II-III disease in the reference arm, 28.7 months among patients who received IP carboplatin, and 27.8 months for patients who received IP cisplatin. Follow-up for overall survival will continue, Walker said.

Toxicity and PROs

Two-thirds or more patients in each arm developed grade 3 neutropenia. Grade 3 thrombocytopenia occurred two to three times more often in the carboplatin groups as compared with the 6.1% rate in the cisplatin arm. Grade 3 hypertension occurred in 12% to 14% of patients in the carboplatin arms and 20.5% of patients randomized to the cisplatin-containing regimen, prompting Walker to suggest that IP cisplatin probably should not be used in combination with bevacizumab. Grade 3 nausea and vomiting occurred in 11.2% of the cisplatin group, two to three times higher than in the other two arms.

Grade 2-plus sensory neuropathy occurred in 21% to 24% of patients in the three arms.

In a second study, researchers analyzed patient-reported outcomes (PROs) -- quality of life, neuropathy, nausea, fatigue, and abdominal discomfort -- showed consistently lower scores among patients in the cisplatin arm, said Lari Wenzel, PhD, of the University of California Irvine Chao Comprehensive Cancer Center. PRO scores did not differ appreciably between the two carboplatin arms, with the exception of slower improvement in abdominal discomfort in patients treated with IP carboplatin.”

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13.  http://www.cancertherapyadvisor.com/gynecologic-cancer/ovarian-cancer-addition-bevacizumab-chemotherapy-longer-survival/article/652503/

[My Note:  This seems contrary to the article quoted above.  However it speaks of “adding” Avastin to a platinum-based therapy MAY be beneficial.  But for me, the risk of adverse side effects of Avastin are not worth survival of 3 more months for ME! Note that the trial above did NOT meet the 6-month PFS requirement.  In discussing this with your medical team, you might want to print out these two articles.  They are still on the web. (Loretta)]

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“April 24, 2017

ADDING BEVACIZUMAB TO CHEMO MAY PROLONG SURVIVAL IN RECURRENT OVARIAN CANCER


Adding bevacizumab to platinum-based chemotherapy may improve survival among women with recurrent ovarian cancer.

Adding bevacizumab to platinum-based chemotherapy may improve survival among women with recurrent ovarian cancer, according to a study published in Lancet Oncology.1

Bevacizumab is emerging as an effective strategy as a first-line or maintenance therapy for recurrent ovarian cancer, which is difficult to treat. The purpose of this trial was to determine if adding bevacizumab to standard chemotherapy and/or secondary cytoreduction could improve survival of patients with platinum-sensitive recurrent ovarian cancer.

This analysis includes the outcomes with bevacizumab treatment; the cytoreduction portion of the study is ongoing…

Median overall survival (OS) was prolonged from 37.3 months (95% CI, 23.6-39.7 months) with chemotherapy to 42.2 months (95% CI, 37.7-46.2) with chemotherapy plus bevacizumab…”

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14.  https://www.avastin.com/patient/mcrc/treatment/possible-side-effects.html

“What are the possible side effects of Avastin?

Possible serious side effects

Everyone reacts differently to Avastin® (bevacizumab) therapy. So it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Your doctor will stop treatment if any serious side effects occur. Be sure to contact your health care team if there are any signs of these side effects…”

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15.  http://www.drugs.com/sfx/avastin-side-effects.html

“Avastin Side Effects - Generic Name: bevacizumab…

Note: This page contains information about the side effects of bevacizumab. Some of the dosage forms included on this document may not apply to the brand name Avastin.

For the Consumer - Applies to bevacizumab: intravenous solution

In addition to its needed effects, some unwanted effects may be caused by bevacizumab (the active ingredient contained in Avastin). In the event that any of these side effects do occur, they may require medical attention.

If any of the following side effects occur while taking bevacizumab, check with your doctor or nurse immediately:


    More common:

  1. Black, tarry stools
  2. bleeding gums
  3. body aches or pain
  4. burning, tingling, numbness, or pain in the hands, arms, feet, or legs
  5. chest pain or discomfort
  6. chills
  7. cloudy urine
  8. convulsions
  9. cough
  10. cracks in the skin
  11. decreased urine output
  12. difficult or labored breathing
  13. dilated neck veins
  14. dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  15. ear congestion
  16. extreme fatigue
  17. fever
  18. irregular breathing
  19. irregular heartbeat
  20. lack or loss of strength
  21. lightheadedness
  22. loss of appetite
  23. loss of heat from the body
  24. loss of voice
  25. mood changes
  26. nasal congestion
  27. nervousness
  28. pain
  29. pain, redness, or swelling in the arm or leg
  30. painful or difficult urination
  31. pinpoint red spots on the skin
  32. pounding in the ears
  33. rapid breathing
  34. redness
  35. runny nose
  36. sensation of pins and needles
  37. slow or fast heartbeat
  38. sore throat
  39. sores on the skin
  40. sores, ulcers, or white spots on the lips or in the mouth
  41. stabbing pain
  42. sunken eyes
  43. sweating
  44. swelling of the face, fingers, feet, or lower legs
  45. swelling or inflammation of the mouth
  46. swollen glands
  47. thirst
  48. tightness in the chest
  49. trouble breathing
  50. unusual bleeding or bruising
  51. unusual tiredness or weakness
  52. vomiting of blood or material that looks like coffee grounds
  53. watery or bloody diarrhea
  54. weight gain
  55. wrinkled skin
  56. yellow skin

Less common:

  1. Abdominal or stomach pain or tenderness
  2. bone pain
  3. difficulty with swallowing
  4. fainting
  5. severe constipation
  6. severe vomiting


Rare

  1. Back pain
  2. blisters
  3. blurred vision
  4. coma
  5. confusion
  6. dizziness
  7. drowsiness
  8. headache
  9. increased thirst
  10. muscle pain or cramps
  11. open sores
  12. pale skin


Incidence not known:

  • Bloody mucus or unexplained nosebleeds
  • hoarseness
  • sudden weakness in the arms or legs
  • sudden, severe chest pain
  • voice changes

Minor Side Effects

Some of the side effects that can occur with bevacizumab may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

 

  1. Acid or sour stomach
  2. belching
  3. bloody nose
  4. change in taste or bad unusual or unpleasant (after) taste
  5. change in walking and balance
  6. clumsiness or unsteadiness
  7. diarrhea
  8. dry mouth
  9. excess flow of tears
  10. hair loss
  11. heartburn
  12. indigestion
  13. stomach discomfort, upset, or pain
  14. thinning of the hair
  15. weight loss


For Healthcare Professionals

Applies to bevacizumab: intravenous solution…”

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