Monday, May 25, 2020

~ 4000 Times the Price of Gold


I made a house call on an 90 year old patient yesterday.  He lives with his wife in an idyllic house surrounded by vernal gardens and a wetland preserve.
 
The patient was presented on VGRD in 2014 with a desmoplastic melanoma of the scalp that measured > 7.5 mm thick.  Since that time, he has done reasonably well.  A metastatic lymph node was excised from the r. preauricular area ~ 4 years ago.  He was doing well until early May, 2020 when he developed right upper quadrant pain.  The ER work-up suggested non-ST-elevation myocardial infarction (NSTEMI) and he was admitted to a local hospital.  There, elevated LFTs were noted and scans confirmed presence of multiple liver masses (largest being 3 cm diameter) and enlarged mesenteric lymph nodes (largest 3.6  cm diameter). A supraclavicular l.n. was biopsied that showed metastatic melanoma.
Significant co-morbidities include recent osteomyelitis (left foot) for which he is currently on oral medication (doxycycline), HTN, gout and the recent NSTEMI, and ischemic cardiomyopathy with a depressed EF (25-30%).
Medications: metoprolol, lisinopril, Plavix, Lipitor, allopurinol, and ASA

He is a high functioning nonagenarian who lives independently with his wife and until the past few months was doing well.

His oncologist is recommending Ketruda (pembrolizumab).  When I spoke with the patient a few days ago he told me that the oncologist said Ketruda was well-tolerated, but when I checked the oncologist’s notes the recorded discussion of side-effects ran 12 lines on the office note. 
Yesterday, the patient gave me a printout he independently made.  After he and his wife read it, and he now has doubts.  His quality of life is good, he enjoys his home, meals, and an occasional dram of Johnny Walker Black… he spoke of quality of life over a few extra months.  He’s done all he wanted to do in life.
We plan to sit down this week in my office and have a more formal discussion.

His metastatic lesions were discovered incidentally as a result of hospitalization for his NSTEMI.  Is this a good sign that pembro will be helpful, or at this time do the risks outweigh the benefits?  When the randomized studies were done with pembro, were nonagenarians with cardiomyopathy or significant co-morbidities excluded?
Your thoughts will be appreciated. 

Postscript: A week after I saw him, he had a PET scan.  The next day, he developed profound weakness. He took to his bed.  Stopped eating and drinking.  He became stuporous and died two days after the scan attended to by his loving wife and a caring nurse.  The day after he died, his oncologist called with the PET scan results.  His liver was entirely replaced with tumor.  He told her that Ketruda was not indicated in such a situation.  He lived reasonably well until two weeks before he died.

Reference
1. Few people actually benefit from ‘breakthrough’ cancer immunotherap
y
By
Nathan Gay and Vinay Prasad. March 8, 2017. Stat Topics.  [We will try to see if the authors still believe this]

2. Alyson HaslamVinay Prasad  Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs. JAMA Netw. 2019 May 3;2(5):e192535.  Free Full Text at PMC.
3. Madhuri Bhandaru, Anand Rotte  Monoclonal Antibodies for the Treatment of Melanoma: Present and Future Strategies. Methods Mol Biol. 2019;1904:83-108.  A Review

 




5 comments:

  1. From Patrick Kenny, Victoria, BC: Re Pembro , I would say most patient do very well and tolerate it , and many
    benefit . Respiratory and g.i symptoms , activation of arthritis , polymyalgia rheumatica , endocrine problems , all controlled with aggressive doses of oral steroids ( oncologists have no fears ) , but I have seen some immunobullous disease , erosive oral lichen planus , Grovers disease but no worse for older
    individuals .

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  2. From Paul and Krystal Jones, Wyoming and Boston Childr3en's Hospital:
    Sounds like a patient would certainly be a good candidate for Keytruda. I would not over interpret the list of side effects given by the oncologist. While there are a myriad side effects, most of them immune related per the mechanism of the drug, for the most part these medications are quite well tolerated, especially in patients who do not have a history of autoimmune disease. Interestingly, in our experience older patients actually have few were immune related adverse effects as opposed to younger patients and therefore tolerate them even better than their younger counterparts. The patient does not have a contraindication that I can see ( would want to discuss his coronary artery disease with his cardiologist before proceeding, however). Sounds like a very reasonable choice, and one that could be significantly life-prolonging (think Jimmy Carter).

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  3. Rob Shapiro, Hilo Hawaii: I had a very similar situation which I had difficulty deciding how to deal with at the time as well. I had a patient with a Very high risk facial squamous cell which had Mohs surgery with clear margins. The oncologists were already involved in the case as consultants from the beginning. They recommended radiation as sole treatment instead of Mohs surgery. The patient had Mohs surgery. Then the radiation oncologist appropriately but less enthusiastically recommended adjuvant Radiation due to the high risk nature of the primary tumor. The patient was adverse to radiation and procrastinated on his decision until it was kind of late for the adjuvant treatment. The patient was concerned about risks to his eye (the large lesion was on his cheek). It was difficult for me to advise him other than for me to say he should follow the recommendations of the radiation oncologist. If I forcefully encouraged treatment, the patient may blame me for the subsequent eye side effects. If I discouraged treatment he or I may regret non treatment. So my course of action was to have him follow the radiation oncologist’s recommendations. Which he did not do. (Dr. Shapiro has a longer comment. We'll ask him to summarize it.)

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  4. Prof. Bhushan KumarJune 02, 2020

    In a person with such a good quality of life – (better than what is expected in most people at this age of 90years) with secondary is the liver -status quo is a better choice. Biological will no doubt produce demonstrable regression of lesion on MRI, hopefully with tolerable adverse drug reaction. But the complications of altered immunity will be difficult to handle – which are likely to happen. Another issue is lack of data on exact duration of remission in given individual.
    So let the patient enjoy as he is doing at the moment.

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  5. From D. Sahni (dermatological oncologist) Boston: "Though I understand the dilemma your patient is having on making a decision, I agree with Dr Alani, and I would go with the oncologist's recommendation on starting pembrolizumab. The anti-PD1 drugs alone are generally much better tolerated than ipilimumab alone or combination immunotherapy (ipilimumab + pembrolizumab). Studies have also demonstrated that monotherapy with anti-PD1 drugs are generally well tolerated even in the elderly with multiple co-morbidities.


    It looks like the oncologist has taken into account all the above and hence opted for single agent pembrolizumab. Of course all drugs have potential side effects, but as Dr Alani mentioned, these can usually be handled by the oncologist who will be following your patient closely. While quality of life is an important consideration, we also have to remember the dismal prognosis of stage IV melanoma, which is mortality within 4-6 months. It is quite typical to be symptom free of melanoma metastases until the very end stage when it's typically too late to do anything, so I would not be swayed by the fact that this was an incidental finding."

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