Some colorectal cancer patients whose tumors had gotten worse on all standard treatments benefited from a combination of Afinitor® (everolimus) and Avastin® (bevacizumab) during a small trial reported at the 2010 ASCO Annual meeting in Chicago.
While no tumors got smaller on the treatment, about half of patients in the Phase II trial had their cancer remain stable for six months or more. Three patients have had stable disease for more than a year.
Seven out of ten patients in the trial had at least one serious side effect. The most common was hypertension, but there were several bowel abscesses or fistulas and one case of bowel perforation. There was one death due to treatment infection.
- All 50 patients in the trial either could not tolerate or had their cancer progress on standard treatments including fluoropyrimidines (5-FU or Xeloda), oxaliplatin, irinotecan, and, if they had normal KRAS, Erbitux or Vectibix.
- 47 had already been treated with Avastin, 42 had cancer get worse while taking it.
- The median number of previous treatments was 4, at least one patient had 8.
28 day treatment cycles included:
- 10 mg Avastin every two weeks by IV
- 10 mg Afinitor orally every day
Serious (grade 3 or 4) side effects included hypertension, increased blood lipids, mouth sores (mucositis), rectal inflammation and sores (proctitis), one bowel perforation, increased blood sugar, fatigue, one serious case of gastrointestinal bleeding, and a bowel perforation. One patient died as a result of a treatment-related infection.
Most patients (68 percent) had some less serious form of mucositis — inflammation or sores — in the mouth, throat, rectum, or vagina.
Two out of three patients (64 percent) had blood lipids increase moderately — cholesterol or triglycerides.
For the 50 patients who were enrolled in the trial:
- Median progression-free survival time was 2.28 months.
- Median overall survival time was 7.87 months.
- 46 percent of patients had disease control that lasted a median of 6.1 months
- No complete or partial responses
- 8 had a minor response lasting median 4.1 months
- 15 had stable disease lasting median 6.7 months
Afinitor is currently approved by the FDA for the treatment of advanced renal cell cancer. It works by inhibiting a protein within the cancer cell called mTOR.
Reporting results of the trial at the American Society of Clinical Oncology Meeting in June 2010 in Chicago, Ivy Altomare and her colleagues concluded,
Bevacizumab plus everolimus has promising activity in refractory metastatic colorectal cancer (even in patients who have progressed on a bevacizumab-based regimen) with a disease control rate of 46%, suggesting bevacizumab plus everolimus may overcome resistance to bevacizumab.
SOURCE: Altomare et al., 2010 ASCO Annual Meeting Abstracts, Abstract # 3535, Phase II trial of bevacizumab (B) plus everolimus (E) for refractory metastatic colorectal cancer (mCRC).
What This Means for Patients
Although Afinitor has been approved by the FDA for patients with renal cell cancer and is on the market, the Phase II trial reported at ASCO this year for colorectal cancer was small. It is certainly too soon to recommend this treatment for colorectal cancer that has progressed on standard treatments.
Larger trials will be necessary to fully discover if combining Afinitor with Avastin is a viable treatment for refractory colorectal cancer. Much more needs to be known about its effectiveness and some of the serious side effects.
Tumor tissue and other specimens were taken from patients in the trial and are being studied now. It may be possible to discover what markers were there in the patients who did well on the combination treatment.
There are several Phase I and II clinical trials that are exploring everolimus in combination with both known drugs and some new ones. Some trials may identify Afinitor as everolimus or RAD100. If your cancer has progressed on all the standard treatments — what is called refractory metastatic colorectal cancer – you may want to talk to your doctor about one of these trials.