CR 477: Infusion 41; new Opdivo results

Today I had infusion no. 41. The oncology waiting area at the Johns Hopkins Weinberg Cancer Center was jam packed, and Dr. Hahn was running more than an hour late on his appointments. I quietly marveled how this waiting room was a small slice of so many across the country filled with people whose lives have been turned upside down by cancer. I sat next to a family with a pre-teen son with leukemia. They drove up from North Carolina, and were talking about their town and county being flooded by the rains from Hurricane Matthew.

Each week I get an email from Inspire containing links to all of the newly posted questions regarding bladder cancer. Typically I spend several hours reviewing and responding to those questions where I might be able to add something helpful. Recently one person asked, "Who here has been DX'd five years ago, and was able to lead an almost normal life?" I responded:

Next month will be my 5 year mark since Dx at age 49
Staged at T2b, micropapillary. Baseline CT in Dec. 2011 was negative for nodal involvement
Neoadjuvant GemCis chemo Jan-March 2012
April 2012 CT showed nodal involvement, abandoned chemo
May 2012 RC with neo. Upstaged to T3, and 12 positive nodes. Watchful waiting.
September 2012 stricture removed from neo
Fall 2012 tried to go back to work, then took disability retirement
Summer 2013 5 weeks in Europe with the family
Aug 2013 distant nodes in shoulder and neck swelling; FNA biopsy confirmed mets BC
Sept 2013 first grandchild born
Sept-Nov 2013 ddMVAC; mets stopped growing for 8 months
Summer 2014 Alaska cruise with friends; family reunions
Fall 2014 Pulmonary embolisms. Ca in neck growing at 1+cm/mo. Updated will and made funeral arrangements.
Feb 2015 started clinical trial with nivolumab (Opdivo); all tumors gone by June.
May 2015 second grandchild born
Summer 2015 Africa safari with family
August 2016 third grandchild born
Currently NED. Still in the trial. Going to Scotland and Ireland later this month.

The next comment was that I should write a book. Others have said the same thing. My blog is a book of days with cancer. I am most fortunate, and grateful, for my continued survival. The past 5 years have been quite a ride, and hopefully it will keep going for a while.

On Tuesday I had another CT scan of my neck, chest, abdomen and pelvis. It's utterly routine now. The next day the nurse called to report that there were no changes from the last scan. No new tumors, no signs of metastatic growth. I've grown rather nonplussed at scan results, since it is only a coarse diagnostic of what's already happening in my body. But still, every negative CT scan is a good thing.

Today Dr. Hahn told me that he had just returned from the 2016 Congress of the European Society of Medical Oncologists (ESMO) in Copenhagen from October 7-11. At that conference Bristol-Myers Squibb released updated data from my clinical trial. The abstract is on page 280 of a 570 page PDF; I've copied the text below:

Nivolumab monotherapy in metastatic urothelial cancer (mUC): Updated efficacy by subgroups and safety results from the CheckMate 032 study 

Background:

Nivolumab has shown promising efficacy and acceptable safety in an open-label, multicenter phase I/II study in patients (pts) with mUC after ≥ 1 prior platinum-based therapy (NCT01928394). Here we report updated efficacy and safety results for the overall population based on additional follow-up and outcomes by differing levels of PD-L1 expression. 

Methods:

Pts with mUC, unselected by PD-L1 expression status, received nivolumab 3 mg/kg IV every 2 wk until progression or discontinuation. Pts who met protocol criteria could continue treatment beyond progression and cross over to nivolumab + ipilimumab. Tumor PD-L1 membrane expression was assessed with Dako PD-L1 immunohistochemical staining. Primary endpoint: objective response rate (ORR; RECIST 1.1); other endpoints: safety, progression-free survival (PFS), overall survival (OS), and duration of response.

Results:

Of 78 treated pts (median age 65.5 years; range, 31–85), 52 received ≥ 2 prior therapies. At a minimum follow-up of 9 months, 23.1% of pts are on monotherapy and 23.1% switched to combination. Treatment discontinuation was mainly due to disease progression. PD-L1 was evaluable in 67 pts (86%). Table shows overall efficacy. In pts with PD-L1 expression ≥ 1% (n = 25) vs <1% (n = 42), ORR was 24% (95% CI, 9.4–45.1) vs 26.2% (13.9–42.0); median PFS, 5.5 mo (95% CI, 1.4–11.2) vs 2.8 mo (1.4–6.5). Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 21.8% of pts; most frequent were ↑ lipase (5.1%), ↑ amylase (3.8%) and fatigue, ↓ neutrophils, rash, ↓ lymphocyte and dyspnea (2.6% each); grade 5 TRAEs occurred in 2.6% (pneumonitis and thrombocytopenia, 1 each). OS by PD-L1 expression and additional subgroup analyses will be presented.

Conclusions:

Nivolumab showed encouraging efficacy and acceptable safety regardless of PD-L1 expression in previously treated, unselected pts with mUC.

Dr. Hahn said that further details were presented at the 2016 ESMO conference. The key takeaways were that about one in every four patients had either a complete response (CR, shrinkage of all tumors to below pathological levels) or a partial response (total tumor burden reduced by 50% or more). In addition to those patients with a good ORR, at least the same number of patients had saw their tumor growth stabilized for at least some period of time. This data is similar to the results for atezolizumab. Based upon this data, Dr. Hahn expects Bristol Myers Squibb to seek expedited approval of Opdivo for metastatic bladder cancer. I'm glad to be in that cohort of 78, and especially grateful that I'm one of the lucky 20 ORR's with a CR.

Jennifer and I are finally settling into a semblance of retirement, now that 1) she has finished her MSW and has elected to be "lightly employed" (one day a week); 2) Garrett graduated from high school, prepared for and left on his mission; 3) Jennifer and I tag-teamed in trips to Utah to help with the birth of our first grandson. Now that a couple of weeks have passed since we finished those activities, we're settling into a comfortable rhythm of not waking to an alarm, catching up on reading, slowing working through the honeydo lists, planning trips, and trying new places to eat. It's a rough life, but somebody's got to do it.

Tonight Spencer and I are going to game 5 of the NLDS, hoping to see the Nationals advance to the LCS. If you see us on TV, be sure to waive. Go Nats!