Immunotherapy for Frail Adults With Common Malignancies: #ASCO18

Although immunotherapy drugs may now provide a treatment option for older patients with cancer who are ineligible for, or whose disease fails, chemotherapy, there are many unanswered questions about the efficacy and adverse effects of immunotherapy in this patient population. Highlighting these knowledge gaps, as well as discussing ways to reconcile those gaps in clinical practice, will be the focus of an Education Session on June 4 titled “Treating Frail Adults With Common Malignancies: Best Evidence to Personalize Therapy.”*

“People should come to the session to get a deep dive into the current existing evidence base for older or more vulnerable adults who are receiving immunotherapy,” said session Chair Ronald J. Maggiore, MD, of the University of Rochester Medical Center. Older adults are often not candidates for standard chemotherapeutic treatments because of comorbidities and poor performance status, Dr. Maggiore said.

The session will focus on non–small cell lung cancer (NSCLC), which Dr. Maggiore will discuss, as well as bladder cancer and lymphoma. The session will also cover immunotherapy recently approved by the U.S. Food and Drug Administration (FDA) for these cancer types, including pembrolizumab for patients with bladder cancer, Hodgkin lymphoma, and NSCLC.¹

However, the clinical trials that led to many of the immunotherapy drug approvals included younger patients than oncologists typically see, Dr. Maggiore said. Most of the patients enrolled in the seminal studies of immunotherapy for NSCLC were in their early to mid-60s, yet 50% of patients diagnosed with lung cancer in the United States are older than 70.² These trials also excluded patients with poor performance status from participation a priori,^3,4 although post-marketing and FDA safety analyses have been somewhat encouraging for single-agent checkpoint inhibitors in older adults or those with poorer performance status, Dr. Maggiore added.

It can be challenging to apply data from these trials to clinical decision-making for older patients, particularly if they have other comorbidities, Dr. Maggiore said. One of the issues is that, as patients age and develop comorbidities, immune function may decline and there may be changes in the tumor microenvironment, all of which could affect the efficacy of immunotherapy drugs.

The session will feature a clinical vignette to illustrate some of the key challenges in deciding how to treat older patients with immunotherapy, Dr. Maggiore said.

Older Patients in Advanced Bladder Cancer Trials

Dr. Ravindran Kanesvaran

During his presentation, Ravindran Kanesvaran, MD, of the National Cancer Centre Singapore, will discuss the characteristics of older patients with advanced bladder cancer who could benefit from immunotherapy drugs.

Patients who are frail or who have poor renal function are ineligible for cisplatin-based chemotherapy, which is the standard of care for advanced bladder cancer. “Thanks to immunotherapy, patients who may not have received the current standard of care can potentially get some treatment that can prolong their life and give them good quality of life,” Dr. Kanesvaran said.

The recent approvals of pembrolizumab and atezolizumab in the first-line treatment of patients with advanced bladder cancer who were cisplatin-ineligible were based on single-arm phase II clinical trials that reported good tolerability and antitumor activity. ^5,6 Moreover, because trial participants were ineligible for cisplatin treatment because of poor performance status or comorbidities such as kidney dysfunction, neuropathy, or hearing loss, they tended to be elderly (median age: 74 and 73 years for the pembrolizumab and atezolizumab studies, respectively).

“Now we know these data specifically apply to older patients with advanced bladder cancer. In general, clinical trial enrollments are biased toward younger populations, and it is a challenge to decide how to extrapolate those data to the older patient,” Dr. Kanesvaran said.

Immunotherapy for Older Patients With Lymphoma in the First-Line and Relapsed Settings

Dr. Raul Cordoba

As is the case with most cancer types, clinical trials of immunotherapy drugs for Hodgkin and non-Hodgkin lymphoma have included few patients older than 65. Raul Cordoba, MD, PhD, MS, of the Fundacion Jimenez Diaz University Hospital, in Madrid, Spain, will review data on PD-1 inhibitors and CAR T-cell therapy for patients with aggressive relapsed lymphoma.

“So far, clinical data on efficacy and safety of immunotherapy in older patients with lymphoma seem to be similar to younger patients, but we need longer follow-up,” Dr. Cordoba said. Research should be conducted to understand the relationship between baseline immune function, as evaluated through a comprehensive immune assessment, and outcomes of immunotherapy in older patients, he said.

Dr. Cordoba will also discuss early clinical studies testing combination nivolumab and brentuximab vedotin as first-line treatment of patients with advanced Hodgkin lymphoma. “This strategy seems to be attractive in older patients with Hodgkin lymphoma who are not candidates for conventional chemotherapy because of frailty or comorbidities,” Dr. Cordoba said.

–Carina Storrs, PhD

*Program information updated as of February 22. For session time and location information, please refer to the ASCO iPlanner on the Attendee Resource Center (am.asco.org/arc).

References:

1. National Cancer Institute. FDA Expands Approval of Pembrolizumab for First-Line Treatment of Non-Small Cell Lung Cancer. cancer.gov/news-events/cancer-currents-blog/2017/fda-pembrolizumab-lung-expanded. Published June 6, 2017. Accessed February 21, 2018.
2. Ferrara R, et al. Cancer Treat Rev. 2017;60:60-8.
3. Reck M, et al. N Engl J Med. 2016;375:1823-33.
4. Brahmer J, et al, N Engl J Med. 2015;373:123-35.
5. Balar AV, et al. Lancet Oncol. 2017;18:1483-92.
6. Balar AV, et al. Lancet. 2017;389:67-76.

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