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 5, 2018 at 7:58 am  #1294802    
catdander forum moderator
catdander forum moderator

Unfortunately in cancer there are more unknowns and unanswered questions than not and that isn’t going to change any time soon. The good news is that researchers are making tremendous strides in closing the gap. That often leaves oncologists and their patients to make decisions based on limited data and individuals’ needs. This type of oncology is sometimes referred to as the ‘art’ or ‘craft’ of oncology because oncologists learn to read patients’ individual circumstances both emotional and physical to create a treatment plan that best fits the individual.

The bottom line is we still don’t know where egfr+ patients fit here, however it does appear from the immature data suggests egfr+ patients may very well receive benefit from consolidation therapy with pdl1 inhibitor after chemo/rads. In figure 2 from the report suggests the small subgroup of 40 or 50 (don’t remember just now) egfr+ subjects did statistically better with the drug but it’s still a pretty small number and probably needs further studying.

I’m not sure but it seems you are worried that taking pdl1 inhibitor now will effect the way a tki may work later. I don’t think anyone would expect a tki to be less effective because someone took a pdl1 prior to recurrence.

I imagine the reason behind the pacific trial having so few non egfr + patients is because there has been little encouragement from the data of other pdl1 and pd1 trials of stage IV single agent and combos but not so much cherry picking for better results.

I wish there were a way to tease out an answer to whether this is the best thing for your wife but there just isn’t. I know how that feels and i’m very sorry. What I do know is that the decision she makes will be the right one and once it’s made and put into action (or not) a mountain of stress will be released. (this last bit is from 9 years experience on grace forums)

All best,
Janine

July 5, 2018 at 8:28 am  #1294804    
JimC Forum Moderator
JimC Forum Moderator

One important factor to keep in mind is that in this study Durvalumab was compared with placebo, rather than an established lung cancer therapy. So although the limited results tend to show that patients may receive a benefit from this consolidation therapy compared to no anti-cancer therapy, the trial was not looking at the question of whether Durvalumab is a better consolidation therapy than, for example, continuing one of the chemotherapy agents. That would be a question for another trial.

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 5, 2018 at 9:38 am  #1294805    

cubety

Jim that is a good point you bring up for further research in regards to other maintenance consolidation like Alimta or something.

Thank you both Jim and Janine for your continued helpful insights as we grapple with decision making near term.

July 5, 2018 at 9:49 am  #1294806    
catdander forum moderator
catdander forum moderator

Jim,
It seems to me the trial is comparing to an established treatment of chemo/rad as a curative treatment so comparing to nothing more is comparing to the standard. No?

July 5, 2018 at 10:02 am  #1294807    
JimC Forum Moderator
JimC Forum Moderator

Janine,

In that sense you’re absolutely correct. The trial presents limited evidence that Durvalumab may be an effective option for consolidation therapy after chemorads, but the opposing argument is that any anti-cancer consolidation treatment would be expected to improve PFS somewhat. But how does it compare to other agents?

It’s similar to the question of whether maintenance therapy just improves PFS because you’re doing something to treat the cancer. The open question any time you measure success by PFS is whether you get improved OS.

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 5, 2018 at 10:55 am  #1294808    

onthemark

Hi Jim, Janine, and Cubety

One thing to note is that Astrazeneca recently announced “Imfinzi significantly improves overall survival in the Phase III PACIFIC trial for unresectable Stage III non-small cell lung cancer” but the specific numbers are not out yet. They will be announced at a medical conference, hopefully in the near future.

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2018/imfinzi-significantly-improves-overall-survival-in-the-phase-iii-pacific-trial-for-unresectable-stage-iii-non-small-cell-lung-cancer-25052018.html

Also based on the earlier published NEJM study finding a huge improvement in PFS, Durvalumab is approved in the NCCN guidelines as consolidation therapy for Stage III lung cancer, unlike any other medication.

There’s a long history of trying other consolidation therapies (chemotherapies and TKIs) but none have had the kind of success that would get them approved by the NCCN, so that is why the standard of care comparison arm in the PACIFIC trial was placebo following definitive chemoradiation.

There’s an exhaustive recent (May 2018) summary of this issue:

Consolidation systemic treatment after radiochemotherapy for unresectable stage III non-small cell lung cancer

https://www.sciencedirect.com/science/article/pii/S0305737218300343

I have access through a library account but otherwise it is behind a pay wall, unfortunately.


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 5, 2018 at 12:07 pm  #1294809    
catdander forum moderator
catdander forum moderator

Lot’s to be impressed by, not the least of which is onthemark’s knowledge. The fact that the trial has already shown an improvement in os is even more impressive especially since this is preliminary data and the numbers can only get better. The os has been proven to be better than any other method of treatment and non treatment for the population. Am I understanding that right? If so wouldn’t this treatment be better than the current standard of care for stage IV as well?
Edit to say I’ve thought about this for minute…For those with stage IV with oligomets might benefit but not so for stage IV who have several mets.

July 5, 2018 at 1:46 pm  #1294811    

cubety

Interesting point catdander on stage IV.

I still feel like placebo in the Pacific study was underperforming after hunting around trying to find more data on typical time to progression in Stage3.

Jim, on maintenance/consolidation it looks like alimta and tarceva are the 2 main ones approved in US. Here was study on Tarceva from awhile back:

https://www.ncbi.nlm.nih.gov/pubmed/?term=Erlotinib+as+maintenance+treatment+in+advanced+non-small-cell+lung+cancer%3A+a+multicentre%2C+randomised%2C+placebo-controlled+phase+3+study

And on pemetrexed/Alimta

https://www.ncbi.nlm.nih.gov/pubmed/19767093

Not a big benefit but wonder if wife as locally advanced could potentially have a maintenance therapy. Onc today said they’d probably just do scans every 3 months without consolidation therapy (edit- IF we did not do Durvalumab). I couldn’t get them into any granular discussion unfortunately with Pacific study, they have lots of patients with different things going on.

  • This reply was modified 2 weeks ago by  cubety.
  • This reply was modified 2 weeks ago by  cubety.
  • This reply was modified 2 weeks ago by  cubety.
  • This reply was modified 2 weeks ago by  cubety.
July 5, 2018 at 6:37 pm  #1294816    

cubety

Interesting small note to Pacific study-

I think the complete response rate was higher in the placebo group than the Durvlaumab group- about 3% of placebo (7 people) compared to about 2% Durvalumab (9 people).

So in terms of % of people, Durvalumab underperformed placebo by 5 people given 2:1 ratio Durvalumab to placebo patients treated. i.e. one would expect twice as many in Durval group comnpared to placebo since there were twice as many patients.

Not sure if maturing study would continue to add to that Durvalumab number?

  • This reply was modified 2 weeks ago by  cubety.
  • This reply was modified 2 weeks ago by  cubety.
July 5, 2018 at 6:57 pm  #1294818    
JimC Forum Moderator
JimC Forum Moderator

I don’t think you can draw any conclusions from that data. When you carve up trial results into such small sub-populations (patients with a complete response), you end up with too small a sample to make the data meaningful.

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 5, 2018 at 9:11 pm  #1294819    

cubety

Yes Jim I completely agree single digit numbers in a 700+ study population are not highly relevant.

It does give a little idea of how lucky few there are to see complete response in fairly short order at that level unfortunately but it does give some hope at least.

I’m still a bit concerned on potential toxicity issues. Given the EGFR+ group as a whole benefited but notgreatly and given PFS for placebo was 5.6 months, this means it could be possible/probable the EGFR+ mutation subpopulation could progress during the 1 year treatment cycle (more than double the time of placebo group to see progression).

This in turn makes me worry my wife could end up[ on Durvalumab only to see at some point during the year progression that would probaby mean a need for a TKI in short order (so switching from Durvalumab to a TKI is quite possible if those things were to happen, e real possibility it seems).

If a TKI was given immediately after a months long exposure to Durvalumab, I wonder if it would have no effect or possibly some of the toxic events shown when both immunos and TKIs were used concurrently.

I’m trying to come up with potential weaknesses to the Durvalumab argument so as to understand potential problems and feel more secure if we go that way by understanding weaknesses as well as strengths since the Dr at SCCA had planned moving ahead with Durvalumab last time we communicated. Currently I feel a little bit uncomfortable to go that route (immuno) and there is a slight chance my wife might be a surgical candidate still.

  • This reply was modified 1 week, 6 days ago by  cubety.
  • This reply was modified 1 week, 6 days ago by  cubety.
July 8, 2018 at 9:13 am  #1294834    

cubety

Does anyone have experience or information on TKIs administered sequentially with immuno (immuno first)? Just wondering if we have recurrence during a 1 year Durvalumab treatment if it would then be something normal to stop the immuno and quickly start a TKI considering both imm No/TKI together have tended to have fairly high toxicity events for whatever reasons. This is meant as a general question for EGFR+ people looking to start Durvalumab but also may specifically help inform us.

This sure is a struggle for decision.

July 8, 2018 at 12:28 pm  #1294846    

cubety

This is older but involves Durvalumab after TKIs had been used, not the other way around but on EGFR+ patients.

http://www.pmlive.com/pharma_news/az_halts_durvalumab_combination_trials_on_safety_grounds_840199

I wonder if there is a granular breakdown of the PACIFIC trial showing which groups had AE events and at what level. With the small amount of EGFR+ Durvalumab takers it may not be wholly representative but might be helpful for general idea.

July 10, 2018 at 12:11 pm  #1294858    
catdander forum moderator
catdander forum moderator

The pacific trial isn’t complete yet but as and I didn’t see a breakdown of av into subgroups but I do recall reading or hearing in one of the previous links in this thread that suggests the egfr group didn’t appear to have more or significantly more av than the other subgroups.

From the ASCO post last Sept., “Treatment-related adverse events occurred in 68% of patients in the durvalumab group compared to 53% in the placebo group. The rate of immune-mediated adverse events was 24% with durvalumab and 8% with placebo. Severe pneumonitis (grade 3/4) occurred in 3.4% and 2.6% of patients on durvalumab and placebo, respectively. Treatment had to be discontinued due to pneumonitis in 6.3% of patients on durvalumab and 4.3% on placebo.

“Overall, there was a slight increase in toxicity in the durvalumab arm, but severe toxicity was similar between groups,” said Dr. Paz-Ares.

He concluded, “Durvalumab is a reasonably well-tolerated treatment with a manageable safety profile that improved progression-free survival by 11 months. PD-L1 inhibition after chemoradiation appears to be a new option for patients with locally advanced, unresectable stage III lung cancer. It will be important to see the impact on overall survival after a longer follow-up.” ” http://www.ascopost.com/News/58042

July 10, 2018 at 1:58 pm  #1294861    

cubety

Thank you catdander for the added focus with the “similar between groups” information. I’m hoping to hear back from oncologist to see if we go durvalumab route that we can start fairly soon.
At infusion, time for snack :). Take care.

July 17, 2018 at 3:02 pm  #1294896    

onthemark

I wish you and your wife all the best on getting your PET scan results tomorrow, cubety.

Jim and Janine, I had good results today with my own scans. No changes since the last time, and I’ve graduated to one year till the next one.


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.

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