CR 461: 40th Infusion, and blessings

Soon after my last infusion I flew to Utah for two weeks. I met my new grandson, Olie, who has gained a pound a week since birth. He's a tank. On Sunday, September 11, we gathered in the historic Ogden 4th Ward Chapel -- the same building where I used to attend stake conferences in the 1970's when I lived in Huntsville, and which now houses one of the Spanish-speaking wards in Ogden where my daughter and son-in-law worship -- for Olie's ritual name and blessing. In LDS congregations, gathering to give an infant a name and a blessing is a tradition that gathers together family and friends to share a joyous occasion. All the men come to the front of the congregation, form a large circle and support the baby and slowly bounce the child up and down while the father gives thanks to God for the new child, states the name, then gives a blessing reflecting the parental hopes and desires. It is one of the purest expressions of love and joy in mortal existence. To celebrate the arrival of child into a loving family, joined by the extended family and friends, is a wonderful way to experience the joy and rejoicing in our posterity.

A few days later we celebrated Rose's third birthday. In the morning, Chelsea and I went to Rose's preschool and watched as she had a little party with her little peeps. Later that evening, we had a low-key family party with a green theme, as she declared that was her favorite color. For much of the rest of my time there, I enjoyed reading books with Rose and Lily, or holding and feeding Olie. Being a grandpa is a great gig.

I also met with a couple of contractors as Jennifer and I further explored the idea of eventually relocating to Utah. We like the idea of building our retirement home where we can age in place. I've done a few sketches of floor plans and elevations. It's fun to think about things like that. At times I catch myself and wonder if I am being arrogant in acting like I might live long enough to do something like that. Usually I am able to settle into a place of gratitude for each day, but living one day at a time makes it hard to make plans. So we are tentatively making plans, and listening closely for God's laughter.

For now, it's all talk. We've decided we need to sell our lake house before we buy any other property. I have this thing about not having more than two mortgage payments at a time. It's unreasonable, but there it is. And so far no one has been willing to pony up the money to by our lake house. And eventually, we'd sell our primary home, but at the way things are going, it probably won't happen before 2018.

Meanwhile, I'm continuing with my clinical trial. Today is my 40th infusion. I'm still undecided whether to end my getting the drug at the two year mark next Spring. My current thinking is that the Nivolumab probably has done everything that it can do to my cancer. In all likelihood, most if not all of my cancer cells with the PD-L1 protein have been killed off by my body's immune system. If there are other cancer cells in my body with different mutations laying low, the drug isn't going to do anything about it. If the cancer comes back with the same PD-L1 protein, then resuming Opdivo (or Tecentriq) will kill those new cancer cells. If the new cancer has another tumor driver, then a checkpoint inhibitor will do nothing to stop it.

Chelsea thought that there might be a risk that the cancer would mutate during the period that I stopped taking the drug. She thought that such a risk might support the idea of continuing with Opdivo therapy, despite the absence of any detectable cancer. It's a good argument. I've done some research into that and asked my doctors about that. The short answer is that we don't know enough about whether mutation from a PD-L1 cancer to a non-PD-L1 cancer is a real risk or not. There mere chance that continuing with therapy could continue to suppress the risk of the cancer returning is a good argument to continuing with the therapy. But for how long? Forever? I don't know. Maybe when I move and can no longer drive to Hopkins every other week. Dr. Hahn says that I should not let the question of whether or not to continue with therapy drive decisions of whether to move or otherwise enjoy life. But the fact is, Opdivo has saved my life by stopping my metastatic cancer. In the absence of any evidence, it's hard to know when to stop taking a drug that has saved your life and might be continuing to save it.

I'm listening to Stairway to Heaven while typing this. Coincidence?

CR 444: Should I continue to ride this horse?

Over the past two weeks, the rash around my lower torso slowly dissipated. I’ve continued to have itching around my neck and upper back. The scars from the poison ivy on my legs are fading. It’s the least amount of itching I’ve had in months. The pharmacy actually had my drug ready ahead of schedule, and I was in and out of the Weinberg infusion center in near- record time.

Before today's infusion (number 39), I spoke with Dr. Hahn and the clinical trial nurse about whether I should continue participating in my clinical trial after the scheduled end of the two-year period. The nurse didn’t think that there would be any problem with that, and said that she would check to make sure that there would be no obstacles. Since the original two years run in February 2017, I have several months to obtain all of the necessary approvals.

Dr. Hahn and I had a long conversation about the pros and cons of continuing therapy. He confirmed my understanding that there is virtually no published data on whether continuing with immunotherapy for more than two years is worth it. Most importantly, there are no data to suggest that continuing with Opdivo will accomplish anything new. The science behind checkpoint immunotherapy is that the drug is supposed to teach my immune system to break through the cancer camouflage by ignoring the PD-L1 protein that the cancer cells were expressing to trick my immune system into not attacking the cancer. With that link broken, my immune system has attacked and destroyed all of my tumors. Dr. Hahn said that, if in fact the drug has worked as it was supposed to, then after it has done its work there is no reason to keep taking the drug. It’s no longer doing anything beneficial.

This view, however, is based upon the assumption that in fact I have no more cancer in my body. No one knows if that is the case. As I understand it, the traditional working assumption of oncologists is that metastatic urothelial cancer circulates systemically in the lymphatic system on a microscopic level, and from time to time may start growing tumors. CT scans are not precise enough to detect microscopic levels of cancer. My CT scans do not show any actively growing tumors, but they still detect a enlarged few lymph nodes where there used to be tumors. Dr. Hahn said that the presence of those slightly enlarged nodes is not clinically significant to him. The radiologists feel obligated to comment upon the slightly enlarged nodes since they were in the same location as the tumors. But he said that there is no evidence that they still have any actively growing cancer cells.

I asked about the fact that my cancer has multiple mutations, and that Nivolumab works on only one of those mutations. Dr. Hahn said that if any of those other mutations were going to going to start growing once the cancer cells that were expressing the PD-L1 protein had been destroyed, he would have expected to see that by now. He could not promise that those other mutations would never start growing, but the fact that they had not as of yet was indicative that they were not metabolically active.

We talked about teasing any information out of the published data, including the preliminary report on the trial I'm in (Checkpoint 032) that was made during the June 2016 ASCO meeting. That report regarding metastatic bladder cancer and nivolumab was limited to only about 80 patients, and showed a overall response of about 25%, and had little data regarding durability for those fortunate few who had complete responses. Another study was five-year review of the earliest patients who received Nivolumab (Opdivo) for metastatic melanoma. That April 2016 study found that 34% of patients were still alive after 5 years, and that there was a durability plateau after 48 months. Another study of the durability of Nivolumab on metastatic melanoma patients (Checkpoint 067) showed that nivolumab alone was almost as effective as nivolumab plus ipilumumab, and had far fewer side effects. Overall response rate was over 40%. Durability was still being measured. We also discussed studies on other checkpoint inhibitors, such as IMvigor 210, a phase II trial of Tecentriq (aka Atezolizumab, or MPDL3280A) on metastatic bladder cancer, which showed that 84% of those patients who responded to that checkpoint inhibitor had ongoing responses.

(84%) who responded to the anti­–­PD-L1 agent had ongoing responses - See more at: http://www.onclive.com/conference-coverage/gu-2016/update-affirms-atezolizumab-activity-in-bladder-cancer#sthash.NR5OeYf9.dpuf

(84%) who responded to the anti­–­PD-L1 agent had ongoing responses - See more at: http://www.onclive.com/conference-coverage/gu-2016/update-affirms-atezolizumab-activity-in-bladder-cancer#sthash.NR5OeYf9.dpuf

 

 

(84%) who responded to the anti­–­PD-L1 agent had ongoing responses - See more at: http://www.onclive.com/conference-coverage/gu-2016/update-affirms-atezolizumab-activity-in-bladder-cancer#sthash.NR5OeYf9.dpuf

I told Dr. Hahn that I had read those reports to suggest that there might be a slight benefit to continuing with immunotherapy. Dr. Hahn said that the studies didn’t support that inference. He said that there was insufficient information of how long the patients stayed on the drug, why they stopped taking the drug, and what type of cancers those who relapsed actually developed. Plus, the sample sizes were small, and the durability data was not specifically spelled out in most. The relevance is further strained by the fact only one of those studies were for bladder cancer. The bottom line is there simply is not any data available that answers my question of how long to continue my therapy. 

Dr. Hahn agreed that the risks to continuing primarily are limited to dermal toxicity, and whether the rashes that I’ve been having will get worse. I asked whether staying on Opdivo would increase the risk that my immune system might get so tired of immunotherapy that it turns on itself and I get an autoimmune disorder. Dr. Hahn said that there was no evidence that the risk of autoimmune disorder increased with time or dosage. If a patient’s immune system was going to overreact to immunotherapy, it likely would do it sooner rather than later. 

I asked whether there were any duration limits either recommended by the manufacturers, or imposed by FDA, on either Opdivo or Tecentriq. Dr. Hahn said there were none. Both had been approved for use on patients who had failed platinum-based chemotherapy, and were approved for therapy until disease progression. He said that, other than studying side effects or potential toxicities, there were no incentives by the manufacturers to limit the duration of use of their drugs. He suggested that eventually institutions and insurance companies would develop guidelines for how long they would administer and pay for these drugs, but those decisions had not yet been made.

Dr. Hahn said that patient peace of mind was the most powerful reason to continue with the therapy. Since the drug had worked and eradicated the metastatic cancer, why stop it? (That’s were I am.) But he said that he could not provide a strong rationale to continue taking Nivolumab once a patient had a durable complete response and had no evidence of disease for more than a year. He noted how the sponsor (Bristol-Myers Squibb) had amended the protocol to allow patients to suspend treatment and resume should the cancer return. He said how he sees many patients who travel great distances and considerable personal expense every couple of weeks to keep taking the drug. For those patients who have had a complete response, he would counsel them that the costs of continuing likely outweighed any benefit. This was especially true now that Tecentriq had been approved for use on metastatic bladder cancer (and Opdivo approval is likely forthcoming), so that if there was any recurrence, patients could resume therapy independent of a clinical trial.

The upshot of all of this is that Dr. Hahn is comfortable with my stopping receiving Opdivo, either in February 2017, or even earlier. If and when I do stop treatment (assuming it’s not because my cancer has come back), I’d still have regular CT scans to see whether I was still cancer-free. Those scans could be done anywhere and could be forwarded to him at Hopkins.

I’m going to mull this over for a while. In the past couple of weeks, Jennifer and I had talked about whether I should continue getting Nivolumab after next February. We’ve also talked about downsizing, and one of the things we discussed was whether it made sense to consider moving away from the DC area and my easy access to Hopkins. According to Dr. Hahn, I shouldn’t let that affect my decision. Jennifer and I had been leaning towards my continuing with the trial for as long as I could. After all, why stop with such a good thing? But if in fact the drug isn’t doing anything more, why stick with it? Maybe I’ve ridden this horse as far as it will go.