CR Day 121: Infusion 17; research on nivolumab durability

Last night I stayed up until 1 am so I could finish reading Neal Stephenson's Seveneves, a cracking good yarn about efforts to preserve humanity following the destruction of Earth. Less than 5 hours later I got up after having wet my bed due to my malfunctioning neobladder. The 50 mg of imipramine that I take each night has helped to decrease the frequency of spontaneous nocturnal voiding, but it still happens enough for me to celebrate each night that I get an uninterrupted sleep. I keep a large waterproof mattress pad underneath my sheet to protect the mattress from stains and smells. After being jolted awake this morning, I quietly left the bedroom so as to not disturb Jennifer. I sat in the hot tub for an hour and saw several shooting stars, reminding me of the meteoric "hard rain" in Stephenson's book. I got out of the hot tub as dawn was breaking and left the top down to cool off as I started my drive to Baltimore.

While waiting for my appointment with Dr. Hahn, I researched the latest data regarding durability of nivolumab. Bristol-Myers has not yet published any data from my trial, or any other Opdivo trial specific to metastatic bladder cancer or other types of metastatic urothelial carcinoma (searches can be run here). Recently published results regarding nivolumab on other types of cancer have been equivocal. For example, an October 20, 2015 Up To Date review of recent advancements in oncology reported the nivolumab had shown promising results in metastatic melanoma and hepatocellular cancer. A September  25, 2015 item in the ASCO Post found that around 20% of heavily pretreated patients with non-small cell lung cancer (NSCLC) had an overall response to nivolumab, and the median duration of response to be about 17 months. Another September 2015 report of a different NSCLC study of nivolumab and ipilumab showed overall responses of between 13 and 39%, with zero complete responses and median progression-free survival of 5-10 months - results the authors called "deep: and "durable." An August 6, 2015 article in Oncology Targets Therapies reviewed the literature regarding nivolumab and metastatic melanoma and concluded that nivolumab was better than conventional chemotherapy, with longer overall response rates and longer durability. At BCAN's August 2015 Annual Think Tank on Bladder Cancer, Dr. Efstathiou summarized the current status of immunotherapy and bladder cancer, including recent nivolumab data.

Armed with this unsatisfactory data set, I asked Dr. Hahn for his views on the likely durability of my complete response to nivolumab. He readily conceded that there was no data directly on point. All we could do for now is to look to how nivolumab was working on other cancers (which is what I had been researching), as well as looking at data from other PD-1 drugs on mets bladder cancer (such as MPDL3280A). But none of that data sheds much light on how long I might have before my metastatic cancer returned. Dr. Hahn said that researchers generally assume that no drug that they are researching will "cure" cancer; instead, in multiple mutation cancers like mine, once the PD-1 avenue was blocked, the cancer likely would start growing using another mutation. But he hastened to add that there was no way to know if, or when, that might happen to me. He sympathized how I was adrift in a sea of uncertainty regarding the durability of my CR, and said that my experience would help inform others who come later. Time will tell.

We then reviewed some amendments to the clinical trial protocol. The most relevant one to me was a new option of voluntarily discontinuing treatment following a complete response, with the right to resume treatment if the cancer returned. If I was to discontinue my every-other-week pattern of infusions, I still would be closely monitored through checkups and CT scans every 6-8 weeks to see whether I had any latent side effects or whether the cancer was growing again. I was given a copy of the new protocol, and we agreed to talk about that option in on November 5 when I will have my next CT scan and infusion. I continued to mull over the yet-unanswered question of nivolumab durability while I received my infusion.

My literature review and questions to Dr. Hahn were prompted by discussions Jennifer and I have been having about the future. I'm slowly starting to lift my eyes to the possibility that I might live longer than the statistics suggested when I was first diagnosed with mets BC (e.g., 90-95% chance of dying by May 2017). But without any data on how others have fared using this therapy, I have no basis to form expectations for how long I may live. I certainly can't assume that I will fit into the conventional mortality tables for a 53 year old white male. According to the Wharton School's longevity calculator, which does not factor in cancer, I'm likely to live well into my 80's, and have only a 5% chance of dying before I'm 60. In fact, those statistics have been inverted for me for the past three and half years: a 5-10% chance that I'd see age 55, let alone age 60. It's now looking more likely that I'll make it to 55. Beyond then: who knows?

Not having an objective basis for my life expectancy continues to leave me wondering how I should make all sorts of decisions. Do I invest for short term protection or long term gains? Do I consider going back to work? Do we sell our lake house after it is rebuilt from the flood caused by a broken pipe? Next year, our nest may be empty. Do we downsize? Do Jennifer and I explore the idea of full-time missionary service for our church? Jennifer and I have kicked around these questions, and have not found an acceptable way to work towards the answers. One approach is, since we don't know what weight to give it, we pretend cancer is not a factor and talk about what we would do. That's led to some interesting discussions, but no resolutions. Time will tell.

median progression-free survival time of 4.9 to 10.6 month - See more at: http://www.cancernetwork.com/wclc-2015/first-line-nivolumab-ipilimumab-demonstrate-deep-durable-activity#sthash.sPfV7yHI.dpuf

median progression-free survival time of 4.9 to 10.6 month - See more at: http://www.cancernetwork.com/wclc-2015/first-line-nivolumab-ipilimumab-demonstrate-deep-durable-activity#sthash.sPfV7yHI.dpudepending upon the demonstrated deep and durable activity