mCRC Trials
The clinical differences between the right and left sided tumors in mCRC.
What is right sided tumors are more frequently characterized by RAS & BRAF mutations positivity; more women, median age at diagnosis is higher and stage tends to be more advanced. Left sided tumors more frequently possess gene expression profiles characteristic of an EGFR inhibitor; low fiber diet, smoking and excessive alcohol.
This trial compared cetuximab plus Folfiri vs. Folfiri alone? What is the MOS for Erbitux in left-sided RAS wild type mCRC in this study? What was the delta?
What is the Crystal Study; the MOS in the left-sided RAS wild type mCRC arm was 28.7 months vs. 21.7 months and the delta was 7 mos.
The common side effect of FOLFOX vs FOLFIRI?
What is neuropathy (oxalplatin) and diarrhea (irinotecan).
The pre-Medications given for Alimta mono or triplet therapy.
What is: Vitamin B12- IM 1 week prior to 1st dose & every 3 cycles after. 400 to 1,000 mcg Folic Acid orally, 7 days before 1st dose of Alimta. Continue during full course of therapy/21 days after last dose of Alimta and Dexamethasone- 4mg by mouth 2x's daily day before, day of and the day after administration of Alimta.
This is a VEGF used to treat mCRC.
What is Avastin?
How do you respond to "I prefer to use Vectibix for RAS wild-type EGFR expressing mCRC because of its bi-weekly dosing."
What is "I appreciate you sharing that perspective and understand how dosing consideration would be important for your patients and your practice. You are correct that the ERBITUX package insert states that ERBITUX infusion is to take place weekly where VECTIBIX states bi-weekly. Would you like me to submit a request to Lilly medical to see if they can answer your question?"
For background knowledge; not for use in detailing: We don’t have information in our label to support the use of ERBITUX bi-weekly. NCCN guidelines includes dosing information on ERBITUX bi-weekly for mCRC.
The percentage of patients that were evaluable for RAS status in the Crystal sub-population post hoc analysis.
What is 65%.
This trial compared cetuximab plus Folfiri vs. bevacizumab plus Folfiri? What is the MOS for the Erbitux arm in left-sided RAS wild type mCRC in this study? What was the delta?
What is the Fire 3 study; the MOS in the left-sided RAS wild type mCRC arm was 38.3 months vs. 28.0 months; and the delta was 10.3 months.
In the Crystal Study acne form rash occurred in this percentage of patients treated with cetuximab and severe acne rash occurred in this percentage of patients receiving cetuximab.
What is acne form rash occurred in 86% of patients and severe acne form rash occurred in 18% patients receiving cetuximab.
The pre-medication given prior to administering Erbitux.
What is premedicate with a histamine-1 (H1) receptor antagonist intravenously 30–60 minutes prior to the first dose or subsequent doses as deemed necessary [see Warnings and Precautions (5.1)].
This is an EGFR used bi-weekly to treat mCRC.
What is Vectibix?
How do you respond to I prefer to use high dose Cisplatin for HNC.
What is "Can your patients tolerate the toxicities associated with high dose cisplatin? Erbitux plus RT also has a NCCN category 1 recommendation to treat HNC patients." "I hope you will still consider Erbitux strongly for ineligible high-cis patients and over weekly cisplatin which has a 2B NCCN category guideline."
The main outcome measure for the Crystal study and the PFS in months for the Crystal regimen vs FOLFIRI alone in the KRAS wild-type sub-population Post Hoc Analysis.
What is Progression Free Survival and what is 9.5 months vs 8.1 months.
This trial compared cetuximab plus Folfox or Folfiri vs. bevacizumab plus Folfox or Folfiri? What is the MOS for the cetuximab arm in left-sided RAS wild type mCRC in this study? What was the delta?
What is the CALGB/SWOG study; the MOS in the left-sided RAS wild type mCRC arm was 39.3 months vs. 32.6 months; and the delta was 6.7 months.
In KN189 what were the top 3 AE's occurring in > or = 15% of the patients in either group.
What is Nausea; Anemia and Fatigue.
What is the Erbitux dosing for mCRC.
What is The recommended initial dose, either as monotherapy or in combination with irinotecan or FOLFIRI (irinotecan, fluorouracil, leucovorin), is 400 mg/m2 administered as a 120-minute intravenous infusion. Need to determine EGFR-expression status using FDA-approved tests & confirm absence of a Ras mutation prior to initiation of treatment with ERBITUX.
These chemotherapy drugs can be given thru an IV or a PORTACATH.
What is FOLFOX and FOLFIRI.
How do you respond to "I use Avastin first line for mCRC regardless of sidedness".
What is "Dr. there are clinical and molecular differences between primary tumors deriving from different regions of the colon."
Present the molecular story and sidedness data.
What does CALGB and SWOG stand for?
What is Cancer and Leukemia Group B and the Southwest Oncology Group.
The Triplet therapy that is in the NCCN guidelines as an option for BFRAF mutant mCRC.
"What is Erbitux/irinotecan/vemurafenib (Zelboraf)."
It seems the marketplace is working hard to find a combination therapy that demonstrates a meaningful difference for a patient (BRAF mutant) that have a very poor prognosis. Studies like this and the Array triplet therapy with recent FDA breakthrough designation status demonstrate how cetuximab continues to be considered an important standard of care for clinical trial and potentially future indications.
As a reminder, this is all off-label – should not be discussed with HCP. However, a nice opportunity to agree that tailoring a treatment specific to a patient’s needs is important and then transitioning to the Erbitux leave behind with Jay and 3 clinical trials.
What is the black boxed warning for Avastin?
What is Gastrointestinal (GI) perforation
The Alimta dosing in KN189 triplet therapy.
What is 500,mg per square meter every 3 weeks with either carboplatin or cisplatin for four cycles. All patients received pre-medication with folic acid, vitamin B12 and glucocorticoids.
The NCCN category for Erbitux in mCRC and for Erbitux in HNC.
What is there is no recommended category for Erbitux for mCRC with the NCCN guidelines. Erbitux has a category 1 NCCN guideline for HNC.
FYI: there are no NCCN Categories for mCRC products.
How do you respond to "I prefer to use Keytruda mono therapy for patients with PDL1 expression over 50 due to toxicities I do not want to incur."
What is "Dr. all of the patients in KN189 were healthy with a PS of 0 or 1, except for 1 patient with a PS of 2 in the triplet arm. The average age in KN189 was 65 years old."
Present the hazard ratio data for the high expressors on page 2085 of the K189.
The purpose of this study is to determine the treatment effect of panitumumab in combination with FOLFOX compared to FOLFOX alone as first line therapy for metastatic colorectal cancer. What was the primary endpoint and results?
What is the Prime study.
The primary endpoint was PFS. The results were Vectibix plus Folfox vs Folfox alone was 9.6 months vs 8.0 months.
Percentage of patients among the cetuximab group that had left sided tumors vs right sided tumors.
and...
Patients were randomized in the CALGB/SWOG 80405 study and
Percentage patients that received FOLFOX vs FOLFIRI in the CALGB/SWOG 80405 study.
What is 71% vs. 29% for cetuximab left vs right sidedness location.
What is 1:1:1 to receive FOLFIRI/mFOLFOX6 + cetuximab (n902=), FOLFIRI/mFOLFOX + bevacizumab (N=899) or FOLFIRI/mFOLFOX6 + cetuximab + bevacizumab (n=533).
What is 73% received FOLFOX and 27% received FOLFIRI in the ITT population..
This is contraindicated for IO therapy?
What is steroids?
FYI: Systemic steroids are contraindicated for IO therapy. In KN21G and KN189 oral steroids were given in both arms as a premed routine for Alimta.
In KN189 how long was the Alimta maintenance dose given.
What is Alimta maintenance dose was mandatory up to 35 cycles for eligible patients.
The name of the trial which compared VECTIBIX to ERBITUX and it showed that they achieve similar patient outcomes involving chemo-refractory patients designed to be a randomized, open-label, non-inferiority study.
What is the ASPECCT Trial promoted by Amgen.
We cannot speak to the ASPECCT Trial; however, if an HCP brings it up, discuss thier first line treatment options for patients with mCRC RAS wild-type. Share with them the post-hoc analysis of sub-population data in the RAS wild-type patient.
Ask what outcome data they consider most important to determine 1st line treatment? (dialogue using the CRYSTAL study including RAS wild type median OS and ORR data.)
How do you respond to I prefer to use Avastin/Folfox vs Erbitux/Folfiri first line for mCRC.
What is "Dr. why do you use Avastin/FOLFOX first line?" Followed by "Do you treat based on sideness and or RAS status?"
Present the clinical/molecular story and the sidedness data.