EGFR+ Exon21 nvr smoke 54 YO Asian female stage 3 taking Durvalumab?

Portal Forums Cancer Treatments / Symptom Management Immune-based Therapy / Vaccines EGFR+ Exon21 nvr smoke 54 YO Asian female stage 3 taking Durvalumab?

This topic contains 75 replies, has 5 voices, and was last updated by  onthemark 2 days, 5 hours ago.

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July 1, 2018 at 9:26 am  #1294724    

onthemark

Thank you Jim for all your insights and taking the time to educate us with lessons from cancergrace.org and Dr. West in particular.

I add a quick note to this discussion up to now that it may not be wholly appropriate to compare ‘mutation simple’ like driver driven lung cancers in Stage IV to Stage III post-radiation. My understanding is that radiation makes cancers more mutagenic, just like cigarette smoking does over the long term (as Jim quoted from Dr. West). What that means is that the cancer accumulates more mutations after treatment with (chemo)radiation. So what were once cancers that could ‘hide’ from immunotherapies become more visible to the immune system and then treatment with immunotherapies can become more effective post radiation or chemoradiation.

I can dig up some references for this too. I mention this because it is something to think about when taking lessons from past clinical trials for your wife’s situation.


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

  • This reply was modified 2 weeks, 4 days ago by  onthemark.
  • This reply was modified 2 weeks, 4 days ago by  onthemark.
July 1, 2018 at 9:29 am  #1294725    

onthemark

ps. This could also be related to the plausible possibility that a treatment order starting with (1) chemoradiation and (2)immunotherapy [possibly concurrent] and then (3)TKI can induce more adverse effects than a different order like (1) chemoradiation (2)TKI and then (3)immunotherapy. This was hinted at in Dr. West youtube video about a recent trial that was discontinued due to early deaths that I linked to earlier in this thread and Dr. West referred to in his reply.


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

  • This reply was modified 2 weeks, 4 days ago by  onthemark.
  • This reply was modified 2 weeks, 4 days ago by  onthemark.
July 1, 2018 at 9:59 am  #1294728    
JimC Forum Moderator
JimC Forum Moderator

onthemark,

It’s certainly true that radiotherapy can cause additional mutations, but as Dr. Julie Brahmer from Johns Hopkins discussed in this podcast the concept that testing for increased mutational burden will result in improved outcomes with immunotherapy is not quite ready for use in routine clinical practice.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

July 1, 2018 at 10:08 am  #1294730    
Dr West
Dr West

Yes, there is certainly some preclinical (lab-based) research and strands of clinical research that support the concept that radiation may induce a greater probability of a good response to immunotherapy, but I agree with Jim and Dr. Brahmer here in saying that this is more a premise than a conclusive finding at this time. To me, it at least provides a reason to not just presume that the situation is exactly the same between the settings of consolidation immunotherapy after chemo/radiation and treatment for metastatic NSCLC.

-Dr. West

July 1, 2018 at 10:27 am  #1294731    

onthemark

Yes I also agree with Dr. West and Jim and was merely pointing out one shouldn’t make the assumption that these two situations are the same for mutation simple cancers, and what some of the consequences might be if they are, in fact, different.

For people who are interested in learning about the immune system and cancer there is a very nice p Nature paper (it’s a bit dated from 2006 but highly cited so you can believe what is written by and large)

Cancer despite immunosurveillance: immunoselection and immunosubversion

https://www.nature.com/articles/nri1936

Nature Reviews Immunology volume 6, pages 715–727 (2006)


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

  • This reply was modified 2 weeks, 4 days ago by  onthemark.
  • This reply was modified 2 weeks, 4 days ago by  onthemark.
  • This reply was modified 2 weeks, 4 days ago by  onthemark.
  • This reply was modified 2 weeks, 4 days ago by  onthemark.
July 1, 2018 at 11:32 am  #1294734    

cubety

Thank you to everyone here helping me learn. I can already go back and see errors I’ve made in posts showing how quickly I’m learning thanks to the very helpful exchange of information with you all.

Wish I had more time to learn more in depth ahead of important decisions to be made for our situation but this information should be very helpful to others in a similar situation going forward.

It helps to see the information relating to BIM protein deletion, I will have to look into that more when time is available. Sounded like a blood test could determine that status but based on onthemark’s continued great information it might not be something to worry about in terms of having negative effect on TKI action.

Thank you JimC too on the point about updated information clarifying why Asian subgroup in particular were performing well in the past on TKIs with the higher EGFR+ mutation prevalence in the subgroup.

I hope you all have a great day and thank you for thisontinuing insightful help.

July 1, 2018 at 1:31 pm  #1294739    

onthemark

A Dec 2017 paper:

“Emerging biomarkers for the combination of radiotherapy (RT) and immune
checkpoint blockers (ICB)”

links to Jim’s and Dr. West’s remarks about biomarkers and summarizes the current state of the art.

RT increases the antigenicity of malignant cells by promoting the upregulation of MHC class I molecules on the cell surface [10,11], by favoring the expression of tumor-associated antigens [12], and (at
least potentially) by enhancing genetic instability or reactivating endogenous retroviruses [13,14]. Moreover, RT boosts the adjuvanticity of cancer cells by at least two mechanisms…

“The potential predictive value of the biomarkers discussed above needs to be studied in patients receiving RT plus ICBs. Indeed, some of the biomarkers that are associated with improved clinical responses to RT or ICB-based immunotherapy may have limited predictive value in the context of combinatorial regimens. As an example, while high PDL1 expression levels are robustly associated with the response of melanoma and NSCLC patients to nivolumab or pembrolizumab (see above), a benefit on progression-free survival was observed irrespective of baseline PD-L1 expression in NSCLC patients treated with chemoradiation followed by durvalumab versus placebo [130]. This result is consistent with the hypothesis that RT can induce PD-L1 expression in the tumor microenvironment, as demonstrated in preclinical settings
[131]…
Here, we will focus our discussion on mechanism-based biomarkers that are emerging as candidates
to specifically predict the response to RT plus ICBs (not necessarily to either of these treatments administered alone).


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

July 1, 2018 at 6:31 pm  #1294752    

cubety

It looks like the hopeful results of the Pacific study for many might lead to some further developments clarifying this line of thinking with possibly mutational burden increased to radiotherapy cancerous areas that might lead to better immunotherapy response shortly after radiation finishes (hope I have that correct)?

Would that hypothesis imply then the idea that simpler EGFR+ homogeneity is not as responsive to immunotherapy than post radiated EGFR+ which could be more heterogenous? Sounds like all this is hypothetical at this point and maybe the Pacific study is a potential piece of evidence to support the idea. Wish I had more time to digest this but have to get back to work.

I’ll have to think when have time over order of treatment with TKI before immuno or the risk of having vice versa based on the real small study stopped early in UCLA. I’m not sure when TKIs would possibly be started post chemorad concurrent treatment (guessing not untila progression is noted?)…

Thank you all again.

July 1, 2018 at 7:07 pm  #1294753    
JimC Forum Moderator
JimC Forum Moderator

Hi cubety,

Sorry if I take you away from work again, but just a couple of points.

First, although eventually we may have sufficient evidence to support the very reasonable hypothesis that radiotherapy can improve the efficacy of subsequent immunotherapy, the history of cancer treatments is replete with examples of concepts that seemed quite logical yet failed in real-world testing, despite initially promising results in preliminary testing.

Second, the full effects of radiotherapy do not become apparent for some time (even a few months) after the course of treatment has ended. That’s because the scarring which radiation can cause can make it difficult to judge what is scar tissue and what are cancer cells when looking at a follow-up scan. In addition, unlike the laser beams used as weapons in sci-fi movies, radiotherapy does not instantly dissolve tumors (would that it were so!) Instead, it alters the DNA of those cancer cells in such a way that they die off or fail to multiply and grow, and that process takes some time. That may be a reason to delay subsequent TKI treatment until it’s clear what is left in the wake of chemorads.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

July 2, 2018 at 8:16 am  #1294760    

onthemark

Hi Cubety

Jim has given you good advise. I am not sure what the protocol period to wait after chemoradiation to get a PET scan is, in the absence of new symptoms, but it might be good to hold off on the PET scan until the after effects of radiation have settled down. I am not sure about this but it is something to look into.

There is another piece of indirect evidence to add to your puzzle, and that is the early discontinuation of clinical trials involving combinations of immunotherapy and TKIs, due to adverse side effects. This can be added to the alarming results Dr. West pointed to in his video that I linked to earlier in his thread. That was also enough to call off a small study.

There is no doubt that immunotherapies change the immune system both in beneficial ways and sometimes in harmful ways, depending on what other medications are involved at the time. It is a bit like playing with fire at the moment though with TKIs. That is my view. Then there is also the possibility of losing an entrance into a promising clinical trial down the road for people who progress on TKIs involving immunotherapy if one had previous exposure to it. Finally there is the expert advise you pointed to originally recommending EGFR+ patients not consolidate with durvalumab.

One more point is that your wife has a predilection to auto-immune disorders, from what you wrote before.

On the other side is a promise of great benefit and potentially increased odds of a cure by taking durvalumab as consolidation as a non-smoker. The evidence for that population is significant, unlike the EGFR+ subgroup.

In the end it comes down to a personal choice that one makes with the knowledge one has at the time.


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

July 2, 2018 at 12:42 pm  #1294765    

cubety

Thank you onthemark and JimC for gathering up the cat herd of our info into a more succinct thought.

I noticed there is beginning to be focus on some that respond negatively to immunotherapies generally with this from 2017:

https://www.targetedonc.com/conference/esmo-2017/study-identifies-subset-of-nsclc-patients-who-experience-hyperprogression-after-immunotherapy

Only 2% were EGFR+ Mutation though. But it highlights potential adverse reaction like in UCLA study. The end part also mentioned possibly studying other treatments to see if they may also have a subset of people experiencing HPD.

Given the FLAURA phase III results regarding osimertinib/Tagrisso as first line treatment for EGFR+ 19 and 21 exon mutations, there is at least potentially a good window of time if my wife’s exon21 mutation doesn’t get wiped out with concurrent rad/chemo therapy underway. With her never smoker status the cancer is possibly more homogenous in nature and lower mutational burden allowing for potential longer good response on inhibitor.

The Pacific study is interesting with the EGFR+ were the worst median responders yet neversmokers had some of the best response so a bit counterintuitive without thinking too deeply on it. You did note the broad ranges in both groups and the smallish sample as possibly being reason for the wide ranges.

Since my wife is EGFR+, that would carry more weight in my mind first before neversmoker status. But since neversmokers tend to have higher EGFR+ mutation it makes me wonder about the breakdown of neversmokers in terms of cancer type.

I’m currently feeling like leaning onthemark’s way with thought there is a good line of TKI treatment if there are micrometasteses that survive current treatment to give us time and avoid possible small but significant risk with EGFR+ immuno treatment reactions if going on Durvalumab and taking into account EGFR+ benefitted but not by a lot with Durval.

  • This reply was modified 2 weeks, 3 days ago by  cubety.
  • This reply was modified 2 weeks, 3 days ago by  cubety.
  • This reply was modified 2 weeks, 3 days ago by  cubety.
  • This reply was modified 2 weeks, 3 days ago by  cubety.
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July 2, 2018 at 1:11 pm  #1294767    

cubety

I have a question after looking at the supplemental data (Asian population for whatever reason fared better I saw, think in S2 supplement chart).

Do people that discontinue treatment still get included in results? Just wondering how things work if results are only based on those that went the whole 12 months or if there is some statistical weighting or something.

Also starting Durvalumab in first two weeks post radiation gave a meaningful boost that looks interesting for followup investigation.

Wishing you thoughts of wellness onthemark with upcoming scans.

  • This reply was modified 2 weeks, 3 days ago by  cubety.
  • This reply was modified 2 weeks, 3 days ago by  cubety.
  • This reply was modified 2 weeks, 3 days ago by  cubety.
  • This reply was modified 2 weeks, 3 days ago by  cubety.
July 2, 2018 at 1:47 pm  #1294772    

onthemark

Hi Cubety,

To answer your question, the NEJM paper defines their sample of patients as:

“Between May 2014 and April 2016, a total of 709 of 713 patients who underwent randomization (99.4%) received at least 1 dose of study drug as consolidation therapy (473 patients received durvalumab and 236 received placebo)”

From this it’s clear they are including all patients who received at least one dose of consolidation therapy (either durvalumab or placebo) in the data they analyze.

And yes, error bars are larger in Figure 2 and similar figures when the subgroup size is smaller and when the spread of results within each subgroup is larger too. The actual true value of benefit has 95% (confidence interval) chance to fall somewhere within the range covered by the error bars. It actually has very small chance to be very close to the central point unless the error bars are very small…

https://www.nejm.org/doi/full/10.1056/NEJMoa1709937

I saw some other reports in the metastatic setting where people who went longer on immunotherapy had higher chance of surviving than people who were treated for less time. See for instance

“In CheckMate-153, among the patients still on nivolumab at 1 year of the study, those who were treated continuously had significantly improved PFS compared with those who stopped nivolumab (hazard ratio [HR], 0.43; 95% CI, 0.25-0.76)”

https://www.onclive.com/conference-coverage/esmo-2017/nivolumab-past-one-year-improves-progressionfree-survival-in-pretreated-nsclc

Thanks for pointing out the results on hyperprogression by immunotherapy. I was unaware of that complication and it is also important to take into account.

Yes, I’ve got my scan tomorrow (fingers crossed) and then have to wait two weeks to see my oncologist to get the result. This wait is unfortunately the norm where I live. So far I have done really well with no recurrence since being diagnosed in October 2015, so I am approaching 3 years now if my luck holds out.


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

July 2, 2018 at 5:09 pm  #1294782    

cubety

Oof, 2 weeks that must be fun. Glad you have history on your side and am hopeful you will keep your winning clear streak going.

Something regarding my wife, they never definitively ruled out the right side cervical node so there is some chance she is not correctly staged. We were told it was a small sample but had lymph tissue so our onc said she felt it was negative and we quickly (thankfully at that point given the 4 1/2 month journey to there) went to chemo and radiation. We later saw the report listed it as indeterminant due to small sample size. At least it wasn’t positive but it isn’t ruled out either.

So I guess it is potentially important to have the PET scan results to see if it is something we need to rule out right away before doing durvalumab if we went that way.
If it still shows metabolic activity beyond other areas I would want a dissection if possible but don’t know if it is possible due to chemo/rad treatments only ending about a week before.. The SUV was 2.6 on cervical node compared to R2 that was 2.7 but I believe the R2 measured slightly larger (basically equal in size) at 0.9 cm if I recall. The primary was 1.8 cm x 1.3 cm I think (going off memory) and 4.1 SUV.

Thank you for your continued help and we are keeping positive thoughts sent your way to sail thru the next 2 weeks without too much dwelling.

July 2, 2018 at 8:04 pm  #1294783    
JimC Forum Moderator
JimC Forum Moderator

onthemark,

Good luck with tomorrow’s scan, and I’m sorry you have to wait so long to hear your doctor’s interpretation of it. We’ll be keeping you in our thoughts.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

July 3, 2018 at 9:30 am  #1294789    

onthemark

Thank you, Jim. I just had the scan (pelvis, abdomen and chest) with and without contrast. If this is unchanged then I’ll hopefully go to low dose yearly ct scans just of the chest as the most likely area of recurrence for my type of lung cancer are the lungs and I am concerned about all the radiation I am being exposed to.

Cubety, I found this article about using PET scans as surveillance following radiation therapy. It might be of interest to you.

“FDG PET-CT scan 3 months after treatment of NSCLC with SBRT was a specific but insensitive test for the detection of recurrence or treatment failure. Serial CT scans should be used for early surveillance following SBRT, whereas FDG PET-CT scans should be reserved to define suspected metastatic disease or to evaluate new abnormalities on CT scan, or for possible reassessment later in the follow-up period after radiation-related inflammation subsides.”

Assessing the Usefulness of 18F-fluorodeoxyglucose PET-CT Scan After Stereotactic Body Radiotherapy for Early-Stage Non-small Cell Lung Cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137590/


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

July 4, 2018 at 9:25 pm  #1294793    

cubety

Hi JimC I was reading over the information you posted on page 2 in discussion here a few days ago. I was trying to get a rough idea how to interpret The figure 2 results in Pacific trial since never smokers had the best overall median numbers I think and EGFR+ had some of the worst which was counterintuitive to me.

From a simple logic point of view it goes against traditional thinking (never smokers having higher EGFR+ mutations yet never smokers having some if best results while EGFR+ had some of worst- although HR for EGFR+ was still roughly 0.75 so a benefit overall).

The real struggles I have are for instance how many AE were from EGFR+ group? And with a little history of TKI and immuno (although at same time) toxicity from previous older studies, how might these EGFR+ responders fare going forward if they need to take a TKI from progression down the road?

Here is a blurb summary from looks like a Korean study:
“Areas covered: Almost all patients treated with EGFR TKIs eventually develop acquired resistance. It has been reported that activation of the oncogenic EGFR pathway enhances susceptibility of the lung tumors to PD-1 blockade in mouse model, suggesting combination of PD1 blockade with EGFR TKIs may be a promising therapeutic strategy. Nivolumab combined with erlotinib was associated with 19% of grade 3 toxicities. The combination of osimertinib plus durvalumab in pretreated or chemo naïve NSCLC patients showed encouraging clinical activity, however, this combination was associated with high incidence of interstitial lung disease (38%), leading to termination of further enrollment. The combination of gefitinib plus durvalumab demonstrated encouraging activity but higher incidence of grade 3/4 liver enzyme elevation (40–70%). The treatment related Grade 3–4 adverse events were observed in 39% of patients when treated with atezolizumab plus erlotinib.”

So in combination TKIs and immuno had high AE. Begs lots of questions for me.

  • This reply was modified 2 weeks ago by  cubety.
  • This reply was modified 2 weeks ago by  cubety.
July 4, 2018 at 10:01 pm  #1294794    

cubety

One concern is if wife takes Durvalumab, a later recurrence would potentially have her taking a TKI with well substantiated general benefits to PFS and OS (for instance FLAURA trial and osimertinib). Yes she could potentially get part of that approximate 0.75 median HR benefit with Durvalumab now hopefully but I can’t find how many EGFR+ made it Thus far thru study and whether they had higher AE incidence. I have several questions about the Pacific study to feel comfortable in logically explaining results to make sense to me personally (like the median difference between never smoker and EGFR+ for example).

Another example, the unknown group performed relatively poorly to others surprisingly to me but maybe they were ‘unknown’ because of unwillingness to biopsy for health risk reasons or age? I’m not sure but older age also underperformed so maybe it’s a possibility.

Also the study was heavily weighted with former smokers and under weighted with never smokers. Could that have had an impact on placebo PFS and OS compared to a more representative weighting of NSCLC people (approx 25% neversmoker)? Then again never smokers responded quite well from median standpoint. I have a bunch of questions probably like a lot of people trying to make tough decisions and just not having a lot of information to go on or time unfortunately.

I do worry a bit for instance if say she needed osimertinib later because of EGFR+ brain mets and might have unforeseen risks if having taken Durvalumab for a year but it is all hypothetical guesswork. That’s one reason it would help follow the subgroups as they move forward in areas such as AE. They probably do have that info somewhere but I was unable to find that kind of granularity.

Thank you very much to you and your wife for all the help you provide people. You both are really good people. Take care.

July 4, 2018 at 11:13 pm  #1294796    

cubety

Interesting, this doctor from Spain apparently involved in the study mentioned median time to relapse is around 9 months:

http://www.ascopost.com/issues/september-25-2017/pd-l1-inhibitor-consolidation-therapy-for-nsclc-new-standard-of-care/?utm_source=TrendMD&utm_medium=cpc&utm_campaign=The_ASCO_Post_TrendMD_0

So if placebo was 5.6 months plus we add the chemo/rad treatment time, wouldn’t that equate to an extra 6 weeks and then up to 45 days after to start? Let’s give a median 30 day start although they were pushing for 14 days and that subset performed well. So 5.6 months plus 1.5 months for chemo/rad plus about 1 month for median time period to start following concurrent chemo/radiation gets us to 8.1 months. About 10% below expected PFS for what doctor mentioned so not a big difference but still about a month.

I wonder how much effect one month would have on the Hazard ratio (if placebo group instead of 8.1 months went to 9 months or what would be equivalent of 6.5 months vs the 5.6 reported).

Given the % difference between 5.6 and 6.5 months, that would be more impactful potentially of HR numbers I would think? Not sure.

I guess another small point would be that one premise of the good response is due to the boost Durvalumab may have in the radiated area from damaged cancer cells as had been briefly mentioned here but it is not a well-supported idea with evidence yet as also mentioned in discussion. Given wife’s potential fairly extensive nodal involvement, it is pretty likely there may be micrometasteses elsewhere outside the radiated field where the EGFR+ mutation cells don’t get hit with radiation so what effect might Durvalumab have on those areas of concern would be another unanswered concern/question. Lots of questions and concerns.

  • This reply was modified 2 weeks ago by  cubety.
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July 5, 2018 at 6:19 am  #1294800    

cubety

Another question I wonder about is if lower SUV score (EGFR+ mutation) cancers have any correlation to length of time that TKIs might work. The thought being a slower metabolic cancer may not divide as fast and therefore inhibitors may work longer generally before resistance happens because division in cancer cells happens at slower rate.

  • This reply was modified 2 weeks ago by  cubety.
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