My wife is about to start her 4th line of treatment, the immunotherapy drug nivolumab. Anyone out there with NSCLC of the subtype mBAC (now known as AIS) undergoing treatment with nivolumab (OPDIVO)? Any feedback about efficacy of the drug, side effects, and so on will be helpful.
In 2014 she was in the TECENTRIQ (atezolizumba) trial but was assigned docetaxel. The expression level was apparently low. I read (PD-L1 Blueprint Project) that the assays (to determine expression levels for PD-L1) for nivolumab, pembrolizumab, and durvalumab, showed similar results whereas the assay used for atezolizumab consistently showed fewer tumor cells compared to the other three.
My wife, 70 yrs. DX Mar 11 NSCLC mBAC (now called AIS). Mar 11 lobectomy left LL & lower UL. Scans: May 11 clean; July 11 bilateral GGOs; Sep 11 more prominent GGOs; Dec 11 worsening GGOs; Feb 12 PET scan further growth, no mets, BRAF positive (V600E);Mar 12 started Carbo-Alimta (6 courses) then Alimta maintenance; initial shrinkage then stable till early 2014; June 14 in trial MPDL3280A (atezolizumab) but was assigned docetaxel stopped Oct 14 after 7 courses side effects too severe. On chemo pause. May 15 started Tafinlar-Mekinist. Initially high fever, chills and Grade 3 uveitis in both eyes. August 15 Tafinlar from 300 mg to 150 mg a day, kept Mekinist at 2 mg a day. Side effects now manageable. Scans early Aug 15 and late Oct 15 showed improved. Latest scan 2/29/16 was very good: GG densities have resolved, no discrete masses are seen: Aug 16 scan still good; Feb 17 scan new growth. Treatment discontinued. About to start immunotherapy drug nivolumab.
Fri, 03/10/2017 - 07:52
I hope someone who has used nivolumab in this context can chime in, because I don't have an good data to share with you on its efficacy in mBAC, but Dr. Evan Lipson of Johns Hopkins presented some good information on managing immunotherapy side effects in this podcast.
I checked out the PD-L1 Blueprint Project assay comparison paper; thanks for pointing out that interesting study. It illuminates the issue of just how slippery the distinction between high and low PD-L1 expression can be, as well as the still-open question of how well does the level of expression predict response to treatment. Different trials use varying cutoffs between high and low, and as the report states, the experience of the pathologist with a particular assay can be a factor. It's certainly doubtful that a patient just above the chosen threshold will fare significantly better than one just below it. Although it may not provide much comfort to you and your wife, who were hoping to get the trial drug, in almost two-thirds of the small number of cases there was agreement between all four assays, and by one practical standard, the assay chosen might only have affected inclusion in about 15% of the cases.
I hope that nivolumab proves especially effective for your wife, and that side effects are minimal and manageable. Please let us know how she is doing with the new therapy.
Fri, 03/10/2017 - 11:33
Thank you Jim for your kind wishes and thanks for the podcast link.
NSCLC is a rather broad definition of LC. There may be quite some meaningful variety among the subgroups that will affect the extent of the response.
Apparently, KEYTRUDA trials were based on narrower parameters for the subgroups than OPDIVO and as such were more successful because they found a better fitting subgroup. (http://blogs.sciencemag.org/pipeline/archives/2016/10/10/keytruda-vs-op…).
We have neither tissue left not can we do another biopsy since too risky after my wife's lobectomy. So KEYTRUDA at this point was not in the picture.
There is also an study on neutrophils (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296654/). I am not schooled in this area but to me it suggests that targeting just NSCLC is painting with too broad a brush. Targeting smaller subgroups may find better fits but then the cost-benefit of such research comes into play.
Over the past six years we have been fortunate that the Carbo-Alimta kept it stable for more than two years, the docetaxel for less than a year. It did work but side effects were too much. The dabrafenib-trametinib combo, once available, was the right choice since it targeted the BRAF mutation. That worked for some 20 months, so here we are now.
Will follow up with progress reports.
Mon, 03/13/2017 - 08:35
I don't think there's any significant experience yet for treatment mucinous BAC/adenocarcinoma with immunotherapy. I have had occasion to treat a few patients with mucinous BAC with immunotherapy over the past couple of years, and the results haven't been particularly impressive. On the other hand, when you're talking about just 3-4 patients, it's too early to say that a new treatment approach won't be helpful. Other than saying that it isn't likely to be amazing for the majority of patients with mucinous BAC, I wouldn't say that the results are necessarily any different for a broader range of NSCLC patients, where the response rate is about 20% overall, and more in the 5-10% range for those with low or no PD-L1 expression. But if it happens to be effective, it can work for a very long time, with few or sometimes even no side effects.
Tue, 03/14/2017 - 11:19
Dr. West, thank you for your feedback.
We hope to eventually generate some helpful and hopefully encouraging feedback. This being her fourth line of treatment means our options were limited.
Reflecting the first line of Carbo-Alimta (which you at the time you favored as well) worked for more than two years. The second line was docetaxel, which did work but she had to stop after seven courses because of the devastating side effects. This was in the atezolizumab trial OAK but she was assigned the docetaxel arm. The third line as the dabrafenib-trametinib combo which was possible because she had the BRAF V600E mutation. This worked for over a year and a half well in excess of the 9 months median.
We are grateful that we have had the good fortune to have workable options over the last six years and gope to add OPDIVO to that list.
Will post our experiences as they occur.
Mon, 06/12/2017 - 14:02
After 6 courses nivolumab CT scan news showed: A more dense consolidation of 1.8x1.5 cm had resolved.
Worsening GGOs, inter/intralobular septal thickening and honeycombing, considered consistent with pulmonary interstitial fibrosis. May be post treatment change, malignancy not excluded.
Sscan was read off-site. My wife's oncologist and clinic's radiologist are inclined to consider this rather inflammatory than interstitial disease which would perhaps be a separate issue altogether.
if the dense consolidation had resolved, suggesting the nivolumab worked, can worsening GGO really be seen as malignant activity?
While not an accurate indicator, her CEA values had started to rise and was 3.5 last Feb, and now 1.2 the lowest since diagnosed 6-1/2 years ago when just below 9.
A mixed bag but malignant activity seems low. Confused abt a good aspect (consolidation gone-drug works) and perhaps not-so-good aspect (worsening GGOs-drug does not work)?
Anyone out there who has experienced this phenomena?
My wife, 70 yrs.
DX Mar 11 NSCLC mBAC (now called AIS).
Mar 11 lobectomy left LL & lower UL.
Scans: May 11 clean; July 11 bilateral GGOs; Sep 11 more prominent GGOs; Dec 11 worsening GGOs; Feb 12 PET scan further growth, no mets, BRAF positive (V600E);Mar 12 started Carbo-Alimta (6 courses) then Alimta maintenance; initial shrinkage then stable till early 2014; June 14 in trial MPDL3280A (atezolizumab) assigned docetaxel stopped Oct 14 side effects too severe. On chemo pause.
May 15 started Tafinlar-Mekinist. Feb 17 scan new growth. Treatment discontinued. Started nivolumab. Jun 17 scan Feb's new growth resolved, worsening GGOs, septal thickening and honeycombing.
Mon, 06/12/2017 - 14:41
Congratulations on the good aspects of the latest scan. As far as the other findings, while it's not uncommon to experience a "mixed response" (in which some areas of cancer shrink while others progress), in this situation there is a fair amount of doubt as to what has actually been imaged. The radiologists reading scans tend to raise every (usually negative) possibility for what appears in the images, so it certainly could be that treatment is working but that it is too early to clearly see the effects in some locations.
If your wife's oncologists are recommending continuing the current, that seems to be a quite reasonable path in light of these scan findings.
Wishing your wife continued good response to nivolumab.
Mon, 06/12/2017 - 17:00
Thanks Jim, your feedback much appreciated.