Nav: Home

Favorable five-year survival reported for patients with advanced cancer treated with the immunotherapy

July 25, 2019

A research team led by experts at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center reports favorable five-year survival rates from the first multidose clinical trial of the immunotherapy drug nivolumab (anti-PD-1) as a treatment for patients whose previous therapies failed to stem their advanced melanoma, renal cell carcinoma (RCC) or non-small-cell lung cancer (NSCLC). The study, which followed 270 adult men and women, reports survival rates substantially higher than what was expected from cancer therapies available in 2008 at the start of the clinical trial, including chemotherapies, kinase inhibitors, biologic therapies, antiangiogenic therapies, biologic therapies and other clinical trials.

With conventional systemic treatments given for patients with stage IV cancers, three-year survival for advanced melanoma was approximately 5%, and the five-year survival rate for NSCLC was 6% at the time the current trial commenced.

By comparison, the results with nivolumab, reported July 25 in JAMA Oncology, show higher than expected rates of five-year survival: 34.2% for melanoma, 27.7% for RCC and 15.6% for NSCLC. Furthermore, in this study, which provides the longest available follow-up on patients with several types of cancer receiving a PD-1 pathway inhibitor, responses were durable.

The new study provides much-needed data on long-term clinical outcomes associated with nivolumab, a drug that blocks the activity of a molecule called PD-1, removing restraints on cancer-killing T cells, says Suzanne Topalian, M.D., professor of surgery, associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and the lead author of the study report.

Topalian says the research team has also identified some clinical and laboratory features in these patients associated with five-year outcomes.

PD-1 on immune cells interacts with the molecule PD-L1 expressed by tumor cells. Cancer cells use this inhibitory interaction to essentially "hide" from the body's immune attack. Nivolumab (anti-PD-1) and other drugs in its class make the tumor cells visible again, restoring the immune system's ability to recognize and kill cancer cells. Much of the science behind anti-PD-1 drugs such as nivolumab (marketed as Opdivo) and pembrolizumab (marketed as Keytruda) was developed by Bloomberg~Kimmel Institute researchers, Topalian notes. The Food and Drug Administration approves both drugs to treat multiple cancer types, sometimes in combination with other therapies or after other therapies fail.

The five-year survival study included 270 patients with advanced melanoma, renal cell carcinoma or non-small-cell lung cancer enrolled at 13 U.S. medical centers, including the Johns Hopkins Kimmel Cancer Center, beginning in 2008 in a phase 1 clinical trial of nivolumab. Patients received different doses of the drug (between 0.1 to 10.0 mg/kg) intravenously in the outpatient clinic every two weeks in eight-week cycles for up to two years.

The patients were previously treated for their advanced cancers--meaning cancers that had spread beyond the reach of surgery and persisted--with 40.4% entering the nivolumab trial having undergone three or more prior systemic therapies. "While all patients had been treated previously, the number of prior treatments did not make a statistical difference in terms of five-year survival in this study," says Topalian.

The study found that patients with larger tumor burdens, or cancers that had spread to the bone or liver, were significantly less likely to survive for five years after starting nivolumab treatment. Furthermore, patients with low immune cell (lymphocyte) counts in their blood at the time nivolumab treatment began were significantly less likely to benefit--certain chemotherapies that patients might have received before entering the trial could have lowered their lymphocyte counts.

However, "patients who entered the trial without any cancer-related symptoms were significantly more likely to survive for five years, compared to those who were experiencing symptoms," Topalian says.

"These findings should help guide patients and their doctors as they consider nivolumab therapy," says lung cancer expert Julie Brahmer, M.D., professor of oncology and co-director of the upper aerodigestive program at the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and the clinical trial's principal investigator. Since the drug's safety was established, she says, it has moved from treating patients who have already received multiple lines of therapy to patients who had only one prior therapy, or even patients who could receive this as first-line systemic therapy for metastatic disease.

In addition, Topalian, Brahmer and colleagues reported in 2018 in The New England Journal of Medicine favorable responses when nivolumab was given before a first surgery for high-risk NSCLC, an approach known as neoadjuvant therapy. "I think we will see an accelerating pace of this kind of research, pushing the earlier use of these drugs," says Topalian.

A notable feature uncovered in the five-year survival study, Topalian says, is that overall survival time was significantly longer among patients who experienced sided effects related to nivolumab, compared to those who experienced no side effects. The midpoint duration of survival was 19.8 months for those with any adverse events and 20.3 months for those with severe adverse events, compared to 5.8 months for those who did not experience any adverse events.

About 10% to 20% of patients experience serious adverse events after taking nivolumab, including inflammatory reactions in the lung or intestines. The most common side effects of nivolumab are fatigue and rash. In most cases, side effects from immunotherapy can be clinically managed to prevent them from becoming life threatening.

Topalian says her team of investigators, and other teams, continue to explore the specific reasons why adverse events appear to be markers of long-term survival in patients taking nivolumab.

"Nivolumab activates immune responses. Although we would like those responses to be directed only at cancer cells, in some cases there is a spillover effect and we encounter immune responses against normal tissues," she says. "Based on the findings in this study, we can reassure our patients that if they develop these side effects, it may very well put them in a better response and long-term effect category. The real issue is whether we can devise treatments to manage these side effects that will not interfere at all with the anti-tumor immune response."
-end-
In addition to Topalian and Brahmer, researchers included F. Stephen Hodi of the Dana Farber Cancer Institute; Scott Gettinger and Mario Sznol of the Yale Cancer Center; David Smith of the University of Michigan; David McDermott and Michael Atkins of the Beth Israel Deaconess Medical Center; John Powderly of the Carolina BioOncology Institute; Jeffrey Sosman of the Vanderbilt University Medical Center; Philip Leming of the Christ Hospital Cancer Center; David Spigel of the Sarah Cannon Research Institute/ Tennessee Oncology; Scott Antonia of the H. Lee Moffitt Cancer Center & Research Institute; Alexander Drilon, Jedd Wolchok, and Richard Carvajal at Memorial Sloan Kettering Cancer Center; and M. Brent McHenry, Fareeda Hosein, Christopher Harbison and Joseph Grosso at Bristol-Myers Squibb.

This study was sponsored by Bristol-Myers Squibb.

Topalian receives grants from Bristol-Myers Squibb, Compugen and Potenza Therapeutics; travel reimbursements from Bristol-Myers Squibb, Dragonfly Therapeutics, Five Prime Therapeutics and Merck; and consulting fees from AbbVie, Amgen, Avidity NanoMedicines, Bayer, Camden, Nexus, DNAtrix, Dragonfly Therapeutics, Dynavax Technologies, Ervaxx, Five Prime Therapeutics, FLX Bio, ImaginAB, Immunomic Therapeutics, Janssen Pharmaceuticals, Medimmune/AstraZeneca, Merck, Pfizer, Rock Springs Capital, and WindMIl outside of the submitted work; receiving stock or stock options from Aduro, Dragonfly Therapeutics, Ervaxx, Five Prime Therapeutics, FLX Bio, Jounce Therapeutics, Potenza Therapeutics, Tizona LLC, and WindMIL; having intellectual property licensed through Johns Hopkins to Bristol Myers-Squibb, Aduro, Immunonic Therapeutics, NexImmune, and WindMIL; and having patents pending for cancer therapy via a combination of epigenetic modulation and immune modulation, checkpoint blockade and microsatellite instability and biomarkers useful for determining response to PD-1 blockade therapy.

Brahmer receives grants and an uncompensated advisory committee/consulting agreement with Bristol-Myers Squibb during this study; personal fees from Amgen, AstraZeneca/MedImmune, Celgene, Genentech, Janssen Oncology, Eli Lilly, Merck and Syndax outside of this study; serves on the advisory board of AstraZeneca, Genentech, Janssen Oncology, Merck and Syndax; and grant support from AstraZeneca/MedImmune and Merck.

Johns Hopkins Medicine

Related Lung Cancer Articles:

AI helps to fight against lung cancer
Lung cancer has been the leading cause of cancer-related deaths in 2015 in United States.
Free lung-cancer screening in the Augusta area finds more than double the cancer rate of previous screenings
The first year of free lung cancer screening in the Augusta, Ga., area found more than double the rate seen in a previous large, national study as well as a Massachusetts-based screening for this No.
Antioxidants and lung cancer risk
An epidemiological study published in Frontiers in Oncology suggests that a diet high in carotenoids and vitamin C may protect against lung cancer.
Lung cancer may go undetected in kidney cancer patients
Could lung cancer be hiding in kidney cancer patients? Researchers with the Harold C.
Hitgen and Cancer Research UK's Manchester Institute enter license agreement in lung cancer
Cancer Research UK, Cancer Research Technology (CRT), the charity's commercial arm, and HitGen Ltd, a privately held biotech company focused on early drug discovery, announced today that they have entered into a licence agreement to develop a novel class of drugs against lung cancer.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Huntsman Cancer Institute research holds promise for personalized lung cancer treatments
New research from scientists at Huntsman Cancer Institute (HCI) at the University of Utah uncovered distinct types of tumors within small cell lung cancer that look and act differently from one another.
High levels of estrogen in lung tissue related to lung cancer in postmenopausal women
Researchers from Kumamoto University, Japan have found that postmenopausal women with multicentric adenocarcinoma of the lung have a higher concentration of estrogen in non-cancerous areas of the peripheral lung than similar women diagnosed with single tumor lung cancer.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Pericardial window operation less efficient in cases of lung cancer than any other cancer
Pericardial window operation, a procedure, where abnormal quantity of malignant fluid, surrounding the heart, is drained into the neighbouring chest cavity, is commonly applied to patients diagnosed with cancer.

Related Lung Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...