Practice Update: Oncology

PracticeUpdate’s Dr. Farzanna Haffizulla spoke with Dr. Petros Grivas about the recently published results

of the phase II trial on atezolizumab in advanced urothelial carcinoma. Dr. Grivas is on the staff of the

Cleveland Clinic in Cleveland, Ohio.

Dr. Haffizulla:

I wanted to first talk about the

results of a phase II study published last

month in

The Lancet

of atezolizumab in

patients with locally advanced and meta-

static urothelial carcinoma who progressed

following platinum-based chemotherapy.

Will you discuss the results of the study and

its impact in treating metastatic urothelial

carcinoma?

Dr. Grivas:

I would be happy to. This is a

landmark study, a phase II trial that was

launched recently. I have to say I was

impressed with how quickly it enrolled

patients. This was a single-arm, not ran-

domized trial of the immune checkpoint

inhibitor atezolizumab, which is directed

against the PD-L1 immune checkpoint, one

of the brakes of the immune system. The

trial tried to evaluate the efficacy, activity,

and safety of atezolizumab in patients who

either had progressed during or after plat-

inum-based chemotherapy or who were

ineligible to receive cisplatin-based chemo-

therapy, which seems to be the standard

of care as first-line treatment for those

patients with metastatic urothelial carci-

noma. The primary endpoint of the study

was to evaluate the overall response rate,

tumor shrinkage, as we say in lay terms;

and, of course, it had a variety of other end-

points. The results of the study that were

recently published in

The Lancet

were spe-

cifically for cohort 2, wherein the patients

had refractory disease, resistant to prior

platinum chemotherapy. Cohort 1, results

for whom are not published yet, are cispla-

tin-ineligible patients. So, in cohort 2, there

was a significant overall response rate with

atezolizumab in patients with platinum-pre-

treated metastatic urothelial carcinoma,

and the response rate appeared to corre-

late with expression of the target, the PD-L1

protein in the membrane of immune-infil-

trating cells.

These results were practice-changing.

The FDA recently reviewed the data and

granted approval to atezolizumab for

patients with advanced urothelial carci-

noma pretreated with and resistant to

platinum chemotherapy, for patients who

received platinum therapy given either

for advanced metastatic disease or peo-

ple who progressed within 12 months after

receiving perioperative platinum-based

chemotherapy either in the non-adjuvant

or adjuvant setting.

Dr. Haffizulla:

I see. Now is this the same infor-

mation that was presented as one of the

ESMO abstracts last year?

Dr. Grivas:

It’s true. The data were presented

initially at ESMO, the European Society of

Medical Oncology, meeting in 2015, and

the updates were presented recently at

the ASCO GU Symposium in 2016 (January

7–9, 2016; San Francisco). The data were

published online in

The Lancet

on March

4, 2016.

Dr. Haffizulla:

So, how does this change the

treatment paradigm? Where does atezoli-

zumab now fit in based on these results in

this patient subset?

Dr. Grivas:

This is a very interesting topic

because, over the last 30 years, there has

not been any new FDA-approved agent for

the management of patients with advanced

metastatic urothelial carcinoma. Right now,

and following the FDA approval, patients

who had progression during or after plat-

inum-based chemotherapy administered

for metastatic disease or who progressed

within 1 year after platinum-based chemo-

therapy given for non-adjuvant or adjuvant

therapy, can be eligible to receive atezoli-

zumab as immunotherapy unless there is a

clear, contrary indication. Contraindication,

for example, would be active autoimmune

disease, patients on immunosuppressive

agents for autoimmune disease, so on and

so forth; however, the majority of patients

are eligible to receive that treatment with-

out the need for any biomarker testing. This

is what we call for all-comers, meaning all

patients could be eligible for that treatment.

Dr. Haffizulla is the Assistant

Dean of Community and

Global Health at Nova

Southeastern University’s

College of Allopathic

Medicine. She practices

general internal medicine in

Davie, Florida, within her own internal

medicine concierge practice.

Reference

1. Rosenberg JE, Hoffman-Censits J, Powles T, et al.

Atezolizumab in patients with locally advanced

and metastatic urothelial carcinoma who have

progressed following treatment with platinum-

based chemotherapy: a single-arm, multicentre,

phase 2 trial.

Lancet

. 2016;387(10031):1909-1920.

www.practiceupdate.com/c/40813

New Data on Immunotherapy for

Bladder Cancer: Part 1

Interview with Petros Grivas

MD, PhD

by Farzanna S Haffizulla

MD, FACP, FAMWA

Dr. Grivas is a medical oncologist in Cleveland, Ohio,

specializing in genitourinary cancer. He is an associate

staff member in the Department of Department of

Hematology/Medical Oncology of the Taussig Cancer

Institute of the Cleveland Clinic Foundation.

Q & A

PRACTICEUPDATE ONCOLOGY