Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult gliosarcoma
Brief summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works after radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
Detailed description
OBJECTIVES: Primary * To determine the overall survival of patients with newly diagnosed glioblastoma multiforme (GBM) with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide. Secondary * To determine the 12- and 24-month progression-free survival (PFS) of patients with newly diagnosed GBM with unmethylated MGMT promoter treated with this regimen. * To assess radiographic response rates. * To perform correlative tissue assays. * To collect safety data on the combination of bevacizumab and erlotinib hydrochloride in patients with newly diagnosed GBM with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide. OUTLINE: This is a multicenter study. Patients undergo radiotherapy (either intensity-modulated radiation therapy or 3-D conformal radiotherapy) once daily 5 days a week and receive oral temozolomide concurrently with radiotherapy once daily for 6 weeks (as planned). Patients whose tumor has a methylated MGMT promoter are removed from study. Approximately 4 weeks after completion of radiotherapy and temozolomide, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment with bevacizumab and erlotinib hydrochloride repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at approximately 30 days and then every 3 months thereafter.
Interventions
DRUGbevacizumab
10mg/kg administered intravenously every 2 weeks
DRUGerlotinib hydrochloride
150 mg/daily orally
Sponsors
M.D. Anderson Cancer Center
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed newly diagnosed glioblastoma multiforme (GBM) or gliosarcoma * Undergoing or plan to undergo treatment with radiotherapy and concurrent temozolomide for 6 weeks * Unmethylated MGMT promoter status must be determined before completing radiotherapy * Tumor must be MGMT negative to receive bevacizumab and erlotinib hydrochloride * Patients who are post biopsy or tumor resection allowed provided a post-operative MRI is done no more than 96 hours after surgery (in order for an accurate assessment to be done post radiotherapy): * Evaluable or measurable disease after resection of recurrent tumor is not mandated for eligibility * Patients who started radiotherapy and temozolomide prior to study entry are eligible as long as the gene methylation status is determined before starting bevacizumab and erlotinib hydrochloride * Radiotherapy plans need to be verified to confirm the treatment plan meets the study requirement based on the PI assessment * No progressive disease based on MRI or CT scan per the investigators assessment PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Life expectancy \> 12 weeks * WBC \> 3,000/μL * ANC \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 10 g/dL * SGOT/SGPT \< 3 times upper limit of normal (ULN) * Bilirubin \< 3 times ULN * Creatinine \< 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * No significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate this therapy, or any disease that will obscure toxicity or dangerously alter drug metabolism * No proteinuria at screening, as demonstrated by either of the following: * Urine protein:creatinine (UPC) ratio \< 1.0 * Urine dipstick for proteinuria \< 2+ OR ≤ 1g protein by 24-hour urine collection * No inadequately controlled hypertension (defined as systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 100 mm Hg) on antihypertensive medications * No history of hypertensive crisis or hypertensive encephalopathy * No New York Heart Association class II-IV congestive heart failure * No history of myocardial infarction or unstable angina within 6 months prior to study enrollment * No history of stroke or transient ischemic attack within 6 months of study enrollment * No symptomatic peripheral vascular disease * No significant vascular disease (i.e., aortic aneurysm or aortic dissection) * No evidence of bleeding diathesis or coagulopathy * No significant traumatic injury within 28 days prior to study enrollment * No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * No serious, nonhealing wound, ulcer, or bone fracture * No known HIV positivity * HIV testing is not required for study participation * No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years PRIOR CONCURRENT THERAPY: * No chemotherapy is allowed prior to starting radiotherapy and temozolomide, including polifeprosan 20 with carmustine implant (Gliadel wafers) * No major surgical procedure or open biopsy within 28 days prior to study enrollment or the anticipation of need for major surgical procedure during the course of the study * No core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment * Concurrent nonenzyme-inducing anticonvulsants allowed * More than 2 weeks (before starting erlotinib hydrochloride and bevacizumab) since prior and no concurrent enzyme-inducing anticonvulsant * No other concurrent experimental agents * Not concurrently participating in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months. | Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival at 12 Months | At 12 months from start of treatment | Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death. |
| Response Rate (RR) | From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease | Response Rate (RR) will be defined as the best response seen during treatment measured by CT/MRI scan every 8 weeks during treatment using McDonald Criteria. CR=Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients off steroids. PR=Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/decreased dose of steroids. Stable/No Response=Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration. Stable/decreased dose of steroids. Progressive disease = 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease), worsening of evaluable disease, new lesions/site, failure to return for evaluation due to death or deteriorating condition. |
| Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles. | Toxicity data for combination treatment of erlotinib and bevacizumab will be collected on day 1 of every cycle (1 cycle = 28 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE |
| Progression Free Survival at 18 Months | At 18 months from start of treatment | Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Tumor Blood Flow Based on MR Perfusion | Prior to study treatment (after surgery, but before radiation), just before study treatment (within 14 days prior to first treatment) and then every 2 cycles during study treatment, where 1 cycle equals 28 days for a maximum of 49 cycles. | Data from consenting patients will be used to assess of changes in tumor blood flow based on MR perfusion using MRI scans. Two scans will be completed prior to treatment on study; the first after surgery buta before radiation, the second within 14 days before starting combination treatment or erlotinib and bevacizumab. Then scans will be completed every 2 cycles during treatment, where one cycle equals 28 days. |
| Gene Methylation Studies (Optional) | At baseline and then plasma only will be collected every odd cycle (1 cycle = 28 days) during treatment for a maximum of 49 cycles. | Tissue and plasma collected from consenting patients in the study will be used to correlate tumor tissue with imaging and outcomes. Tissue will be collected before treatment on study begins and plasma will be collected the first day of treatment (before treatment) and every odd cycle after that, whilst on study treatment. Tissue and plasma analysis will be correlated with patients imaging results and response to to treatment |
Countries
United States
Participant flow
Recruitment details
The study was ready for accrual March 12, 2009 with an accrual goal of up to 50 patients. The first patient was enrolled on July 7 2009. Accrual was suspended on July 29 2010 and reopened on March 30, 2011. The study was closed permanently on November 03, 2011 with an accrual of 48 patients treated on study after screening 115 patients.
Pre-assignment details
Registration is a two step process. ICF signed, tissue sent off and MGMT promoter methylation status determined eligibility. Patients with unmethylated MGMT promoters will be complete the second registration step and be treated on study. Patients with methylated MGMT promoters will not be treated on study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Erlotinib and bevacizumab
Bevacizumab: 10mg/kg administered intravenously every 2 weeks
Erlotinib hydrochloride: 150 mg/daily orally | 115 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow up Until Death | Alive at last data collection | 4 |
| Follow up Until Death | Withdrawal by Subject | 1 |
| Reached 1st Response/2 Cycles | Progressive Disease | 1 |
| Reached 1st Response/2 Cycles | Withdrawal by Subject | 1 |
| Registration to Study | Determined to have methylated MGMT | 67 |
| Went on to be Treated Cycle 3 | Adverse Event | 1 |
| Went on to be Treated Cycle 3 | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 82 Participants |
| Methylated/unmethylated MGMT promoter Methylated MGMT promoter | 67 Participants |
| Methylated/unmethylated MGMT promoter Unmethylated MGMT promoter | 48 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 109 Participants |
| Region of Enrollment United States | 115 participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 43 / 48 |
| other Total, other adverse events | 48 / 48 |
| serious Total, serious adverse events | 15 / 48 |
Outcome results
Primary
Overall Survival
Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact.
Time frame: From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months.
Population: 2 patients were not evaluable - 1 patient withdrew consent and 1 patient completed less than 1 cycle of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Overall Survival | 13.2 Months |
Secondary
Progression-free Survival at 12 Months
Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
Time frame: At 12 months from start of treatment
Population: Two patients were determined not to be evaluable (one patient withdrew consent from the study and one patient completed one cycle)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Progression-free Survival at 12 Months | 32 percentage of patients |
Secondary
Progression Free Survival at 18 Months
Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
Time frame: At 18 months from start of treatment
Population: Most patients had progressed before the 18 month time point. Data was not collected for PFS at 18 months.
Secondary
Response Rate (RR)
Response Rate (RR) will be defined as the best response seen during treatment measured by CT/MRI scan every 8 weeks during treatment using McDonald Criteria. CR=Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients off steroids. PR=Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/decreased dose of steroids. Stable/No Response=Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration. Stable/decreased dose of steroids. Progressive disease = 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease), worsening of evaluable disease, new lesions/site, failure to return for evaluation due to death or deteriorating condition.
Time frame: From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease
Population: Two patients were determined not to be evaluable (one patient withdrew consent from the study and one patient complete one cycle of treatment only)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Response Rate (RR) | Partial Response | 12 Participants |
| Erlotinib and Bevacizumab Combination Treatment | Response Rate (RR) | No Evaluable Disease (NED) | 2 Participants |
| Erlotinib and Bevacizumab Combination Treatment | Response Rate (RR) | Complete Response | 4 Participants |
| Erlotinib and Bevacizumab Combination Treatment | Response Rate (RR) | Stable/no response | 28 Participants |
| Erlotinib and Bevacizumab Combination Treatment | Response Rate (RR) | Progressive Disease | 0 Participants |
Secondary
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population
Toxicity data for combination treatment of erlotinib and bevacizumab will be collected on day 1 of every cycle (1 cycle = 28 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time frame: From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles.
Population: All patients that received at least one dose of study drug were evaluable for toxicity. Data for grade 3 and 4 toxicities during treatment were collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Hyberbilirubinemia | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Cerebrovascular ischemia | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Dehydration | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Dermatology/Skin | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Rash/desqyamation | 5 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Hypertension | 3 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Fatigue | 3 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Leukocytes | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Lymphopenia | 12 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Heartburn | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Pain (not otherwise specified) | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Pain abdomen | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Pain head/headache | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Bowel perforation | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Hypophosphatemia | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Rash/acneform | 2 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Syncope | 1 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Thrombosis/embolism | 2 patients |
| Erlotinib and Bevacizumab Combination Treatment | Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population | Wound complication | 1 patients |
Other Pre-specified
Changes in Tumor Blood Flow Based on MR Perfusion
Data from consenting patients will be used to assess of changes in tumor blood flow based on MR perfusion using MRI scans. Two scans will be completed prior to treatment on study; the first after surgery buta before radiation, the second within 14 days before starting combination treatment or erlotinib and bevacizumab. Then scans will be completed every 2 cycles during treatment, where one cycle equals 28 days.
Time frame: Prior to study treatment (after surgery, but before radiation), just before study treatment (within 14 days prior to first treatment) and then every 2 cycles during study treatment, where 1 cycle equals 28 days for a maximum of 49 cycles.
Population: This was an optional portion of the study that patients could participate in. Data was not collected or analyzed for this outcome measure.
Other Pre-specified
Gene Methylation Studies (Optional)
Tissue and plasma collected from consenting patients in the study will be used to correlate tumor tissue with imaging and outcomes. Tissue will be collected before treatment on study begins and plasma will be collected the first day of treatment (before treatment) and every odd cycle after that, whilst on study treatment. Tissue and plasma analysis will be correlated with patients imaging results and response to to treatment
Time frame: At baseline and then plasma only will be collected every odd cycle (1 cycle = 28 days) during treatment for a maximum of 49 cycles.
Population: This was an optional portion of the study for consenting patients. No data was collected and analyzed for this outcome measure.
Post Hoc
Median Progression Free Survival
Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
Time frame: From the start of treatment and every 2 cycles, where 1 cycle equals 28 days, during treatment. Median follow up at time of data was 33 months.
Population: Two patients were not evaluable
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Median Progression Free Survival | 9.2 months |
Post Hoc
Overall Survival at 12 Months
Overall Survival (OS) is measured from start of treatment until death from any cause.
Time frame: At 12 months from start of treatment
Population: Two patients were not evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Overall Survival at 12 Months | 54.5 percentage of patients |
Post Hoc
Overall Survival at 24 Months
Overall Survival (OS) will be measured from start of treatment until death of any cause
Time frame: At 24 months from first treatment
Population: Two patients were not evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Overall Survival at 24 Months | 32.8 percentage of patients |
Post Hoc
Progression Free Survival at 6 Months
Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
Time frame: At 6 months from start of treatment
Population: Two patients were not evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib and Bevacizumab Combination Treatment | Progression Free Survival at 6 Months | 66.3 percentage of patients |