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

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)