It's been a busy few days. On Sunday, we attended a memorial service for my good friend Cynthia, who passed away earlier this month 16 days after being diagnosed with a particularly virulent form of cancer. Her death was a sobering reminder of how little we know about to treat cancer, and how different each form of cancer. To speak of cancer as a single disease is like speaking of all humanity as a single life.
On Monday, my youngest son Garrett received his missionary call from the LDS Church. Mormon young men and women are encouraged to volunteer to serve as missionaries, and Garrett has been preparing for some time for his mission. He will depart on July 6 to serve for two years in the Utah Salt Lake City East mission, which stretches from the eastern part of Salt Lake City through Park City and Summit County and into western Wyoming. (A blog with a map is here.) Garrett is relieved that he will not be in a really hot area and will not be exposed to strange foods (although he does not yet know about Rocky Mountain Oysters). He will leave two weeks after he graduates from high school. He's a bit excited and a bit overwhelmed and a bit apprehensive, which shows good judgment on his part.
On Tuesday, I spent the day on Capitol Hill as part of BCAN's advocacy to members of Congress and their staffs. I and others affected with bladder cancer met with the staffs of Virginia's elected officials. We were asking that bladder cancer be made a permanent part of the Congressionally Directed Medical Research Program (CDMRP), and that $4 million from that program be set aside for bladder cancer research. Although bladder cancer is the fifth most common form of cancer in the US (and the fourth most common in veterans), it is only 27th in the level of federal cancer funding. The CDMRP is one of the best ways to ensure federal funding is directed towards this often-ignored disease. After meeting five different staffers who were pleasantly noncommittal, my last meeting was with Senator Crapo of Idaho. To his credit, he immediately understood the basis for our request and agreed to make it happen. That will encourage so much more research and will dramatically advance the understanding of bladder cancer.
Today, I'm at Hopkins. Before my regular appointment with Dr. Hahn, I met with Stephanie Greenberg, who with her husband is spearheading the creation of the Greenberg Bladder Cancer Institute. She said how she was a loyal reader of my blog, and how it had helped her and her husband after he was diagnosed with bladder cancer. I thanked her for all that she and Erwin have done and continue to do in advancing the research and treatment of bladder cancer. The Greenberg Institute is the first in the nation to focus solely on bladder cancer, and Stephanie outlined an ambitious vision to make it happen. We're fortunate to have such an enthusiastic and generous person take such concrete steps to change the landscape around this disease.
When I met with Dr. Hahn, I told him about my meeting with Stephanie as well as Sen. Crapo's promise regarding the CDMRP. Dr. Hahn was elated, since he was working with a number of his fellows on applying for grants. He said that having a dedicated pot of money for bladder cancer research would dramatically help increase the desirability of working on that cancer. "You made may day!" he said.
I also asked about the ASCO abstracts. He said that the data for nivolumab and the other checkpoint inhibitors showed between a 19% and 31% overall response rate. These were of people who had failed chemotherapy, and had no other treatment options. Most were looking at imminent death. From that perspective, the level of response was tremendous. It underscored how fortunate I have been to have had a complete response. Dr. Hahn said that at the ASCO meetings next week, researchers would be discussing the factors of when immunotherapy seemed to work better, including positive testing for PD-L1 and lower co-morbidities. He said that there was a tremendous amount of interest in this recent research, and expected attendance to be standing room only. I told him that I looked forward to hearing more about it at our next appointment in two weeks.
In contrast to everything else, my infusion with nivolumab was routine. Strap me in, hook me up, pump it in. Rinse and repeat every two weeks.
This weekend we'll gather with family and friends at our lake house. Reconstruction is finally done, and we're looking forward to spending the Memorial Day weekend there. We've put it on the market and hope that another family will enjoy the location as much as we have.
Thursday, May 26, 2016
Wednesday, May 18, 2016
CR 331: Initial report on my nivolumab clinical trial
This afternoon ASCO released the abstract of the first analysis of my clinical trial with nivolumab (Opdivo) on patients with metastatic bladder cancer (mUC, for metastatic Urothelial Cancer). A total 78 mUC patients were enrolled in the nivolumab-only portion of the trial. As of the point that this data was collected, two-thirds of the patients had dropped out of the trial because their disease had progressed. (A third dropped out within the first three doses.) Only one-quarter of the participants had an Overall Response, which includes stable disease, partial response (e.g., total tumor shrinkage of 25-50%), or complete response (total tumor shrinkage to below pathological levels). Among those who responded, the median duration of response has not been established, because a few patients (like me) continue to have a complete response. Very few patients had serious side effects.
Although the authors state that overall survival data are encouraging, these data are not as promising as I had hoped. While there is no breakdown within the ORR between stable, partial, and complete responses, if we assume that it breaks down to one-third each, that means that only about 8% (or 5 or 6 of the 78 patients) had a complete response. Thus, my ongoing complete response, with no evidence of disease, puts me at the far end of the bell curve. I feel extraordinarily fortunate and humbled to be in that minority of patients having the best possible response.
The text of the abstract is as follows:
Background: Minimal antitumor activity of existing therapies and the observation of immune dysfunction in bladder cancer have prompted evaluation of immunotherapy in this malignancy. Nivolumab (fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody) monotherapy has shown survival benefit in patients (pts) with melanoma, lung cancer, and renal cell carcinoma. Here, we report efficacy and safety of nivolumab monotherapy in pts with mUC after ≥1 prior line of platinum-based therapy in an open-label, multicenter phase I/II study (NCT01928394). Methods: Pts (unselected by PD-L1 expression status) with mUC received nivolumab 3 mg/kg intravenously every 2 weeks until progression or discontinuation. Primary endpoint was objective response rate (ORR; RECIST 1.1). Other endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of 78 treated pts (median age 65.5 years; range, 31–85), 65.4% had received ≥2 prior therapies. At a median follow-up of 213 days (range, 22–499), 33.3% of pts remain on therapy; primary reason for treatment discontinuation was disease progression. Median number of doses was 8.5 (range, 1–34); 70.5% received >4 doses. Efficacy findings are shown in the table. Outcomes by PD-L1 expression will be included in the presentation. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 20.5% of pts; most frequent were increased lipase and increased amylase (3.8% each) and fatigue, decreased neutrophils, and dyspnea (2.6% each). Grade 5 TRAEs occurred in 2.6% of pts (pneumonitis [n=1] and thrombocytopenia [TTP; n=1]). No grade 3 or 4 pneumonitis or TTP was reported. Conclusions: Nivolumab monotherapy demonstrated promising efficacy and acceptable safety in previously treated, unselected pts with mUC. OS data are encouraging. Clinical trial information: NCT01928394
Although the authors state that overall survival data are encouraging, these data are not as promising as I had hoped. While there is no breakdown within the ORR between stable, partial, and complete responses, if we assume that it breaks down to one-third each, that means that only about 8% (or 5 or 6 of the 78 patients) had a complete response. Thus, my ongoing complete response, with no evidence of disease, puts me at the far end of the bell curve. I feel extraordinarily fortunate and humbled to be in that minority of patients having the best possible response.
The text of the abstract is as follows:
Background: Minimal antitumor activity of existing therapies and the observation of immune dysfunction in bladder cancer have prompted evaluation of immunotherapy in this malignancy. Nivolumab (fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody) monotherapy has shown survival benefit in patients (pts) with melanoma, lung cancer, and renal cell carcinoma. Here, we report efficacy and safety of nivolumab monotherapy in pts with mUC after ≥1 prior line of platinum-based therapy in an open-label, multicenter phase I/II study (NCT01928394). Methods: Pts (unselected by PD-L1 expression status) with mUC received nivolumab 3 mg/kg intravenously every 2 weeks until progression or discontinuation. Primary endpoint was objective response rate (ORR; RECIST 1.1). Other endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of 78 treated pts (median age 65.5 years; range, 31–85), 65.4% had received ≥2 prior therapies. At a median follow-up of 213 days (range, 22–499), 33.3% of pts remain on therapy; primary reason for treatment discontinuation was disease progression. Median number of doses was 8.5 (range, 1–34); 70.5% received >4 doses. Efficacy findings are shown in the table. Outcomes by PD-L1 expression will be included in the presentation. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 20.5% of pts; most frequent were increased lipase and increased amylase (3.8% each) and fatigue, decreased neutrophils, and dyspnea (2.6% each). Grade 5 TRAEs occurred in 2.6% of pts (pneumonitis [n=1] and thrombocytopenia [TTP; n=1]). No grade 3 or 4 pneumonitis or TTP was reported. Conclusions: Nivolumab monotherapy demonstrated promising efficacy and acceptable safety in previously treated, unselected pts with mUC. OS data are encouraging. Clinical trial information: NCT01928394
| Parameter | Nivolumab All treated pts (N=78) |
|---|---|
| ORR (confirmed), % (95% CI) | 24.4 (15.3−35.4) |
| Median PFS, months (95% CI) | 2.8 (1.5−5.5) |
| Median OS, months (95% CI) | Not estimable (NE) (7.0−NE) |
| 12-month OS rate, % (95% CI) | 51.6 (37.0−64.5) |
| Median time to response, months (SD) | 1.5 (2.1) |
| Median DOR, months (95% CI) | NE (5.5−NE) |
Tuesday, May 10, 2016
CR 323: CT, 31st infusion, radioactive biceps
The past two weeks have really sucked for reasons unrelated to my cancer. Last week, one of my best friends died 16 days after being diagnosed with leiomyosarcoma. I'm still dealing with her loss and likely will write about Cynthia when I am in a better state of mind. But meanwhile, I find some comfort in the monotony of my ongoing infusions with nivolumab.
During my 30th infusion two weeks ago, I apparently picked up a virus from the hospital. The next day I woke up with a sore throat. It soon blossomed to full head cold, with congestion, cough, runny nose, etc., but no fever, chills, or lung congestion. It's been difficult to shake. Two weeks later I still have post-nasal drip and am coughing up phlegm.
I get CT scans of my neck, chest, abdomen, and pelvis every 12 weeks as part of my clinical trial. Kaiser has agreed to do those scans as part of its ongoing cooperation with Hopkins. So last Tuesday I went to Kaiser's Tyson's Corner facility for my scan. They usually don't access ports for scans, so the tech placed an IV in my left arm. When he started to push the contrast into my vein, I immediately felt pain and hollered for him to stop. He had blown my vein and was pushing the barium into my arm. So he switched arms, placed the IV, and started the pump. The same thing happened. By this time, he was visibly upset with himself. Rather than have him blow a third vein, I asked that he get the senior nurse in to do the job, which she did. I asked about the contrast that had been pumped into each of my arms, and she said to not worry, it would soon be absorbed. Meanwhile, she said with a smile, I would have radioactive biceps. It was the nicest thing anyone had said about my physique in some time.
The results of the scans, by the way, was nominal. No change from the last few scans. I have a few nodes scattered around my chest that are visible on the scan, but none are of pathological significance. No new growth, and no sign of metastatic activity. Hurrah for Opdivo! Hurrah for Bristol-Myers Squibb!
Last Saturday was the annual BCAN walk. This is the fifth year that there has been a Team KBROS at the walk. Because I was focused on helping Cynthia and Walter as much as possible, I was unable to send out any emails asking for donations, so the only contributions were the result of word of mouth. So here's your chance: click on the link and donate now. (I'm looking at you, mom!) At the walk we brought Nephi, our standard poodle, and put him in an orange t-shirt which we found made him a magnet for anyone with a camera. The skies cleared for the firs time on weeks, and we enjoyed a nice stroll around our national mall. Dr. Apolo, who I credit with saving my life by getting me into this trial, spoke of the exciting advances in research. She spoke how the FDA (which had employees in attendance) was soon likely to approve new therapies for bladder cancer. When that day comes, it will be the first new drug approved for metastatic bladder cancer in over 30 years. It's been too long. And there is such a long way to go.
When entering Hopkins today, I was handed a mask. All patients, visitors, and employees are being asked to wear masks. Apparently a virus has swept through the hospital, and they are trying to manage it. I told Dr. Hahn of my ongoing congestion, and he ordered a rapid influenza test. A video from 1990 shows how the test is conducted. Yeas, it's that bad. In the infusion wing, I was placed into an isolation room pending the results of the test. I prefer the peace and quiet instead of hearing the latest inane daytime shows on another patient's TV. Why people don't bring and use earphones is just another example of either lack of awareness or selfishness.
Speaking of Dr. Hahn, I confirmed with him that the results of my specific clinical trial cohort would be published on May 18, and discussed at ASCO on June 5. The report is titled Efficacy and safety of nivolumab monotherapy in metastatic urothelial cancer (mUC): Results from the phase I/II CheckMate 032 study, and is Abstract 4501. This report is limited to the monotherapy arm of my trial, e.g., patients who just received nivolumab. I'm curious to find out the ORR, PR and CR rates. The data for the patients who received combination therapy (nivolumab and ipilimumab) have not yet been compiled and will not be released this month.
I also was told that Stephanie Greenberg wanted to meet with me the next time I am at Hopkins. She and her husband, Erwin, recently donated $15 million to Hopkins to create the Johns Hopkins Greenberg Bladder Cancer Institute. Apparently she has been following my blog. I won't be able to make it to the dedication ceremony this Saturday, but will look forward to meeting her. I am grateful to the Greenberg's generosity, as well as the dedication of all of the health care professionals who continue to work in the bladder cancer community.
During my 30th infusion two weeks ago, I apparently picked up a virus from the hospital. The next day I woke up with a sore throat. It soon blossomed to full head cold, with congestion, cough, runny nose, etc., but no fever, chills, or lung congestion. It's been difficult to shake. Two weeks later I still have post-nasal drip and am coughing up phlegm.
I get CT scans of my neck, chest, abdomen, and pelvis every 12 weeks as part of my clinical trial. Kaiser has agreed to do those scans as part of its ongoing cooperation with Hopkins. So last Tuesday I went to Kaiser's Tyson's Corner facility for my scan. They usually don't access ports for scans, so the tech placed an IV in my left arm. When he started to push the contrast into my vein, I immediately felt pain and hollered for him to stop. He had blown my vein and was pushing the barium into my arm. So he switched arms, placed the IV, and started the pump. The same thing happened. By this time, he was visibly upset with himself. Rather than have him blow a third vein, I asked that he get the senior nurse in to do the job, which she did. I asked about the contrast that had been pumped into each of my arms, and she said to not worry, it would soon be absorbed. Meanwhile, she said with a smile, I would have radioactive biceps. It was the nicest thing anyone had said about my physique in some time.
The results of the scans, by the way, was nominal. No change from the last few scans. I have a few nodes scattered around my chest that are visible on the scan, but none are of pathological significance. No new growth, and no sign of metastatic activity. Hurrah for Opdivo! Hurrah for Bristol-Myers Squibb!
Last Saturday was the annual BCAN walk. This is the fifth year that there has been a Team KBROS at the walk. Because I was focused on helping Cynthia and Walter as much as possible, I was unable to send out any emails asking for donations, so the only contributions were the result of word of mouth. So here's your chance: click on the link and donate now. (I'm looking at you, mom!) At the walk we brought Nephi, our standard poodle, and put him in an orange t-shirt which we found made him a magnet for anyone with a camera. The skies cleared for the firs time on weeks, and we enjoyed a nice stroll around our national mall. Dr. Apolo, who I credit with saving my life by getting me into this trial, spoke of the exciting advances in research. She spoke how the FDA (which had employees in attendance) was soon likely to approve new therapies for bladder cancer. When that day comes, it will be the first new drug approved for metastatic bladder cancer in over 30 years. It's been too long. And there is such a long way to go.
When entering Hopkins today, I was handed a mask. All patients, visitors, and employees are being asked to wear masks. Apparently a virus has swept through the hospital, and they are trying to manage it. I told Dr. Hahn of my ongoing congestion, and he ordered a rapid influenza test. A video from 1990 shows how the test is conducted. Yeas, it's that bad. In the infusion wing, I was placed into an isolation room pending the results of the test. I prefer the peace and quiet instead of hearing the latest inane daytime shows on another patient's TV. Why people don't bring and use earphones is just another example of either lack of awareness or selfishness.
Speaking of Dr. Hahn, I confirmed with him that the results of my specific clinical trial cohort would be published on May 18, and discussed at ASCO on June 5. The report is titled Efficacy and safety of nivolumab monotherapy in metastatic urothelial cancer (mUC): Results from the phase I/II CheckMate 032 study, and is Abstract 4501. This report is limited to the monotherapy arm of my trial, e.g., patients who just received nivolumab. I'm curious to find out the ORR, PR and CR rates. The data for the patients who received combination therapy (nivolumab and ipilimumab) have not yet been compiled and will not be released this month.
I also was told that Stephanie Greenberg wanted to meet with me the next time I am at Hopkins. She and her husband, Erwin, recently donated $15 million to Hopkins to create the Johns Hopkins Greenberg Bladder Cancer Institute. Apparently she has been following my blog. I won't be able to make it to the dedication ceremony this Saturday, but will look forward to meeting her. I am grateful to the Greenberg's generosity, as well as the dedication of all of the health care professionals who continue to work in the bladder cancer community.
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