Five Clinical Highlights From AACR Annual Meeting (Part 1)

The American Association for Cancer Research (AACR) Annual Meeting 2021 is mostly a jamboree of basic research and early-stage clinical study presentations, but some of the presentations feature clinical data that can change oncology practice.

This has especially been true in recent years, when the number of phase 3 trials of cancer immunotherapies began to mushroom and investigators and their sponsors have competed for high-profile sessions at major clinical oncology meetings.

Medscape Medical News has highlighted five clinically significant ― or potentially important ― studies presented during part 1 of the AACR 2021 annual meeting, which was held virtually this year.

Part 2 of the AACR 2021 annual meeting will be held May 17–21 and will feature education sessions, methods workshops, and other session types outside of research findings.

Practice Changer in Metastatic Uveal Melanoma

Results from the first randomized controlled trial to be positive for overall survival (OS) in metastatic uveal melanoma were described as "seminal and practice changing" by discussant Caroline Robert, MD, PhD, of Gustave Roussy and Paris-Saclay University, in Paris, France.

The phase 3 trial explored first-line use of the experimental therapy tebentafusp (Immunocore) and how it compares with immunotherapy or chemotherapy for patients with metastatic disease.

In the 378-patient trial, patients were assigned in a 2:1 ratio to receive either tebentafusp (n = 252) or investigator's choice of pembrolizumab (n = 103), ipilimumab (n = 16), or dacarbazine (n = 7).

At a median follow-up of 14.1 months, OS was significantly longer for patients who received tebentafusp than for patients in the investigator's-choice arm ― 21.7 months and 16.0 months, respectively. The estimated 1-year OS rate was 73.2% in the tebentafusp arm and 58.5% in the standard-therapy arm (hazard ratio [HR], 0.51; P < .0001).

Target-mediated or cytokine-mediated adverse events were the most common side effects with tebentafusp. These included pyrexia (76%), pruritus (69%), and rash (83%), which decreased in frequency and severity after the first three to four doses.

Although cytokine release syndrome was common (89%), the rate of grade 3–4 cytokine release syndrome was very low (1%), the meeting heard.

Tebentafusp is a protein that redirects T cells to kill gp100-expressing tumor cells. Because the T-cell receptor binding domain only recognizes a specific gp100-derived peptide presented on HLA-A*02:01, tebentafusp can only be used to treat patients with this HLA type, explained lead study author Jessica Hassel, MD, of University Hospital Heidelberg, in Heidelberg, Germany.

The manufacturer announced recently that tebentafusp (IMCgp100), used for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma, has been granted breakthrough therapy designation by the US Food and Drug Administration (FDA).

Lung Cancer Disappears Before Surgery

The immunotherapy nivolumab (Opdivo) has secured a plenitude of approvals in many different types of advanced cancer and is now being tested in early-stage disease, like many other anti-PD-1 and anti-PD-L1 agents.

New phase 3 trial data suggest that nivolumab, administered before surgery for patients with resectable non–small cell lung cancer (NSCLC), may be a fitting use for the checkpoint inhibitor.

Results from the CheckMate 816 trial show that the rate of pathologic complete response (pCR) improved from 2.2% with standard chemotherapy alone to 24% when nivolumab was added to chemotherapy.

This difference translated into an odds ratio of 13.94 (P < .0001) for achieving a pCR, reported Patrick Forde, MBBCh, from the Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland. pCR was the primary endpoint and was defined as complete regression in both the primary tumor and lymph nodes.

Study discussant Jhanelle Gray, MD, from the Moffitt Cancer Center, Tampa, Florida, pointed out that a meta-analysis of 32 neoadjuvant chemotherapy-based studies in NSCLC showed clear associations of pCR and major pathologic response to both OS and event-free survival.

However, Gray said that the findings need to be confirmed in the setting of immunotherapy, because at times, radiographic findings do not correlate with histologic findings with these agents.

Improved Survival in Kids With "Horrendous" Tumor

Recurrent or progressive high-grade glioma is "a horrendous disease that hasn't really responded to anything," according to Howard Kaufman, MD, director of the Oncolytic Virus Research Laboratory at Massachusetts General Hospital, Boston, Massachusetts.

Kaufman was asked to comment on a small, phase 1 study of an experimental immunotherapy that contains a genetically altered version of herpes simplex virus type 1 (HSV-1).

The oncolytic virus product, known as G207, stimulates an immune response and kills tumor cells.

In the clinical trial, the product was infused directly into the brains of 12 patients aged 7 to 18 years who had glioma. It yielded a median overall survival of 12.2 months, which is more than double the median of 5.3 months seen in historical control patients.

The study from Gregory K. Friedman, MD, of the University of Alabama at Birmingham, and colleagues was published simultaneously online in The New England Journal of Medicine.

One oncoloytic viral therapy is already on the US market. Talimogene laherparepvec (Imlygic) is an oncolytic HSV-1 therapy that was approved in 2015 by the FDA for local treatment (ie, injection directly into the skin lesion) of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurs after initial surgery.

Made-to-Order Treatment for Metastatic Melanoma

Patients with metastatic melanoma whose disease continues to progress after treatment with the highly touted immunotherapy and targeted agents have few treatment options remaining. One that may work is customized cell therapy based on T cells extracted directly from tumor tissue.

One such product, called lifileucel, is individually made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from the patient's cancerous lesions.

This approach differs from other cell-based therapies, such as CAR T-cell therapy, which utilizes T cells collected from the patient's blood.

Results from a phase 2 trial of lifileucel conducted in 66 patients with previously treated unresectable or metastatic melanoma yielded an objective response rate of 36.4%. Three of the 24 responses were complete; 21 were partial.

After a median follow-up of 28.1 months, the median duration of response was not reached and ranged from 2.2 to >35.2 months, said Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville, in Louisville, Kentucky.

Meeting discussant Philip Greenberg, MD, of the Fred Hutchinson Cancer Center, Seattle, Washington, observed that customized cell therapy with TILs is not new ― it has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, he commented that "generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells."

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise, Greenberg observed. This study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes, he said.

Healthy Lifestyle in Men at High Risk for Prostate Cancer

Adhering to a healthy lifestyle may offset the heightened chance of lethal prostate cancer for patients with high genetic risk scores, according to results from a large US cohort study.

Lead study author Anna Plym, PhD, of Harvard School of Public Health, Boston, Massachusetts, noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors. Common single-nucleotide polymorphisms (SNPs) account for a substantial proportion of prostate cancer susceptibility.

A polygenic risk score derived by combining information from 269 SNPs is "highly predictive" of prostate cancer, added Plym, citing recent research.

The investigators used this score to quantify the genetic risk for prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

Also, the investigators classified the men using a validated lifestyle score.

Using follow-up data that extended as far as 22 years, the team found that adherence to a healthy lifestyle did not decrease the risk for prostate cancer overall (HR, 1.01; 95% CI, 0.84 – 1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk for lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs 6%).

Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay and MedPageToday and had bylines in WashingtonPost.com, MSNBC, and Yahoo. Email: nmulcahy@medscape.net and on Twitter: @MulcahyNick.

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