Revisiting TKI (Afatinib or Tarceva) +chemo combination - 1259131

No, there is still no critical mass of interest and certainly no real evidence to support any combination of an EGFR inhibitor with anything else except perhaps for afatinib/cetuximab for acquired resistance to Tarceva (erlotinib) or Iressa (gefitinib), and this combination itself remains of unclear benefit in larger studies.

Good luck.

-Dr. West

Dr. West

wasn't there some studies that showed patients who had developed resistance to Tarceva was able to have longer progression free survival when they stayed on Tarceva and have chemo added to their regimen. the theory is that chemo will kill off the resistant cells and Tarceva will continue to kill off the sensitive cells.

thanks

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sb,

Dr. West has said this about gamma delta therapy: "I know essentially nothing about these alternative therapies and personally don’t have a lot of enthusiasm for them." - http://cancergrace.org/lung/topic/nodule-appeared-two-months-after-surg…

The Memorial Sloan Kettering Cancer Center website has this to say about Avemar (wheat germ extract): http://www.mskcc.org/cancer-care/herb/wheat-germ-extract

JimC
Forum moderator

I agree with Dr West. I would humbly submit to you that those who insist on adding anything to Tarceva at this point are 'selling something', or have some agenda.

Tarceva in combination with first-line chemotherapy was tested in the Phase III TRIBUTE trial with 1,059 patients. It is rarely mentioned, because it was a negative trial. Another Phase III trial called TALENT with 1159 patients asked the same question, it was still negative. The combination did add toxicity though.

Regarding adding Avastin to erlotinib, it seems the evidence does not support that either. The Phase III BeTA trial with 638 patients did not meet its primary endpoint, but addition of Avastin did increase toxicity. It may be that Roche/Genentech wouldn't mind if practitioners adopted off-label prescribing of Tarceva during chemotherapy, but I'm not confident that this combination is in the best interests of the patient.

Regarding adding immunotherapy like anti-PD1 to EGFR TKI, that is just beginning to be studied. There are a couple trials that are testing the safety of Tarceva with immunotherapy. Some small trials have tested vaccines like HS101 with Tarceva. I believe a Phase III trial called TIME is testing the a viral cancer antigen vaccine with Tarceva maintenence. I understand that one anti-PD1 trial has included ~10 patients with Tarceva treatment at the same time. There is a trial in China combining a T-cell product immunotherapy with Iressa. There may be more of these trials I don't know about, or that may open soon.

Yes anti-PD1 only available on clinical trials. It is not given as a vaccine. Rather, anti-PD1 is a protein that binds another protein, which then stimulates your immune system. Hope this helps.

Unfortunately, after multiple lines of chemo and targeted therapy, there aren't any clear options that can be anticipated to be beneficial. The only agent that she hasn't received that has been studied in previously treated patients and known to improve survival is Taxotere, and even that is really studied almost exclusively as a second line therapy.

Beyond that, it's mere speculation of what to try, though a clinical trial with a novel agent is always a strong consideration if one is available.

Good luck.

-Dr. West

There's only so much real data on the subject of 3rd plus lines of therapy. Most studies on approved drugs and approved uses are 1st and 2nd line. So when planning for 3 plus lines of treatment doctors must use their own judgement. There's talk about what doctors do, what doctors only use in trials, and "ASCO talk". ASCO talk is usually about treatment that's still in the research phase.

Another way to look at what may be appropriate for your mum is to look at what drugs she has not progressed on. From your signature it looks like she switched around a lot without progressing. It's reasonable to go back to a drug that one's not progressed on.

On progression, http://cancergrace.org/lung/2013/01/23/acquired-resistance-algorithm/

I hope this helps

Excuse me for reactivating this old thread of 2013. We are now at a cross road where there is progression at the Lung and Adrenal Gland after 8 months of Afatinib+cetuximab, as well as multiple brain mets that have been stable for sometimes, presumably credit to Afatinib. The plan is to move to Carboplatin+Alimta as Tagrisso is not available yet here. However, the concern is the control of brain mets that we think may be less likely to hold by chemo. Our Oncologist is suggesting to continue Afatinib at low dose while we get on chemo. I think this combination is not well studied and there is a warning of Pancytopenia by Dr. Christine Chung from John Hopkins Sidney Kimmel Cancer Centre. (http://journals.lww.com/oncology-times/Fulltext/2015/04100/Warning_abou…), but another article seems to report some benefits and acceptable risk profile from the combination of Afatinib with Paclitaxel at Lux-Lung 5 trial.
I would appreciate any input from Cancergrace on the feasibility of combining Afatinib with Chemo.
Thank you.
NJ

I would caution against using preclinical data to make clinical decisions. The information hopey2009 cites was published 6.5 years ago, and the concept of combining afatinib/cetuximab was actually the focus of greater interest 5 years ago than it is today. It is not an advocated approach by any group of lung cancer experts and not widely practiced, for good reason: It is very difficult for patients to tolerate, typically with very severe skin side effects, and it doesn't work nearly as well as a mouse model might suggest.

The fact is that it is very common for promising early leads to not pan out as effective and tolerable treatment choices, which is why thoughtful experts don't make recommendations based on work that hasn't been vetted in sufficiently large clinical trials.

Though I completely understand that advanced cancer can lead to a sense of urgency, there are potential negative consequences to going well beyond the evidence. We go to great pains to have myself, the moderators, and GRACE faculty not make medical recommendations to people who are not our patients and to be circumspect in the language we use describing what we feel are the best approaches, including clarifying the difference between clear evidence and our judgments. And in the case of myself and most of the other GRACE faculty, we are board certified, nationally to internationally recognized experts in our fields, but we still don't overstate our perspective.

Accordingly, I would ask all readers to KNOW YOUR SOURCE -- know how much expertise they have and whether what they make recommendations are based on are major clinical trial results or speculations based on early research and best guesses.

And I must ask hopey5000 to refrain from making recommendations to our readership. First, unless I'm mistaken, you aren't qualified to make medical recommendations to anyone anywhere. Second, because your recommendations are based on speculation, not actual evidence.

-Dr. West

As Dr. West stated, we don't make specific recommendations about treatment choices, for two main reasons. First, there are legal implications in giving advice to GRACE users who are not patients of any of the GRACE faculty. Perhaps more critically from a medical point of view, without full information about a patient's situation, including scan images, results of biopsy testing, lab results, clinical examinations and prior treatment, we would be making recommendations based only upon the small slice of information that can be provided in a forum of this type. Such recommendations would be of little value, much like a pop psychologist trying to diagnose a patient's mental health situation on the basis of a two-minute telephone call (with apologies to Dr. Frazier Crane).

GRACE exists to educate, not to be a substitute for local, hands-on medical care. The idea is that a well-informed patient or caregiver will be better equipped to understand and participate intelligently with his or her medical team in discussions about treatment choices. During my wife's illness, I often brought information from the GRACE site or other sources to her oncologist's attention. Discussion with him sometimes showed these were viable options or reasonable concerns, at other times there proved to be good reasons why they weren't, based on a full understanding of her medical condition. Either result made us feel that we were fully participanting in the decision-making process. From day one, that has been the goal of Dr. West and GRACE.

JimC
Forum moderator