Nivolumab in NSCLC: Indication of major added benefit for under 75-year-olds

November 18, 2015

Nivolumab is an anti-tumour drug from the group of monoclonal antibodies. It has been available since June 2015 under the trade name Opdivo for adults with advanced melanoma, and since July 2015 under the trade name Nivolumab BMS also for adults with metastatic squamous non-small cell lung cancer (NSCLC) after prior chemotherapy.

The German Institute for Quality and Efficiency in Health Care (IQWiG), which in October 2015 had already found an added benefit of the drug for patients with advanced melanoma, now examined in another dossier assessment whether nivolumab also offers an added benefit over the appropriate comparator therapy in the treatment of NSCLC.

According to the findings, there is an indication of major added benefit of nivolumab over the appropriate comparator therapy docetaxel for under-75-year-olds in relatively good general condition, and a hint of a non-quantifiable added benefit for over-75-year-olds in relatively good general condition. For patients in worse general condition, an added benefit is not proven due to a lack of study data.

Comparator therapy depends on general condition

The Federal Joint Committee (G-BA) distinguished between two treatment situations in its commission: In patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, and possibly 2, the benefit or harm of nivolumab was to be compared with docetaxel as appropriate comparator therapy.

For patients for whom docetaxel is not indicated due to their worse general condition (ECOG PS 4, 3, and possibly 2), the appropriate comparator therapy was to be the so-called best supportive care, i.e. treatment tailored to the individual patient's needs, which aims to alleviate symptoms such as pain and improve quality of life.

Informative data on the outcome 'overall survival'

Since the manufacturer presented no data on the second research question in its dossier, an added benefit of nivolumab is not proven for patients with a higher ECOG PS in comparison with the appropriate comparator therapy best supportive care.

For the first research question, data from the study CA209-017 were available, a randomized, open-label, active-controlled approval study on the comparison of nivolumab with docetaxel in patients who had already had platinum-based chemotherapy and whose general condition corresponded to ECOG PS 0 or 1.

The risk of bias was low both at study level and for the outcome 'overall survival'. In other outcomes such as severe adverse events or treatment discontinuation due to adverse events, the risk of bias was high, however. No evaluable data were available on further benefit outcomes such as health-related quality of life.

Gained life expectancy depends on age

The results for the outcome 'overall survival' depended on age. Patients under the age of 75 years had a statistically significant advantage of nivolumab. Their median survival time was 9.5 months, which is 3.5 months longer than in the docetaxel arm of the study (6 months): an indication of major added benefit. Over-75-year-olds, in contrast, had no advantage, and shorter overall survival cannot be excluded. Hence in older patients, there is no hint of an added benefit of nivolumab for this outcome.

No suitable data were available for the outcome categories 'morbidity (symptoms and health status)' and 'health-related quality of life'; an added benefit is therefore not proven.

Advantages in side effects

In the outcome category 'side effects', there was a hint of lesser harm from nivolumab in each case for treatment discontinuations due to adverse events and for severe adverse events. Greater or lesser harm was not proven for serious adverse events (SAEs).

Only qualitative interpretation was possible of the data on specific side effects because of the different observation durations in the study arms: There was a hint of lesser harm from nivolumab in each of the non-severe specific adverse events 'myalgia', 'peripheral neuropathy' and 'alopecia', and an indication of lesser harm in blood and lymphatic system disorders.

Under-75-year-olds: indication of major added benefit

Overall, there is an indication of major added benefit of nivolumab in comparison with the appropriate comparator therapy for patients with ECOG PS 0 or 1 in whom docetaxel treatment is indicated and who are younger than 75 years.

For patients who are older than 75 years, an added benefit is not proven for the outcome 'overall survival'. Overall, the marked positive effects of nivolumab in the outcomes 'treatment discontinuation' and 'severe side effects' and in the specific adverse events resulted in a positive conclusion also here: In patients with ECOG PS 0 or 1 who are 75 years of age or older, a hint of a non-quantifiable added benefit of nivolumab versus the appropriate comparator therapy docetaxel remains.

G-BA decides on the extent of added benefit

This dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website », published by IQWiG, provides easily understandable German-language information.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on » If you would like to be informed when these documents are available, please send an e-mail to »

Institute for Quality and Efficiency in Health Care

Related Nivolumab Articles from Brightsurf:

MD Anderson researchers present immunotherapy advances at Society for Immunotherapy of Cancer Annual Meeting
Promising clinical results with combination treatments for patients with melanoma and lung cancer highlight immunotherapy advances being presented by researchers from The University of Texas MD Anderson Cancer Center at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) .

Immunotherapy combination improves outcomes in advanced kidney cancer
An immunotherapy agent combined with a tyrosine kinase inhibitor drug significantly improved progression-free survival and reduced the risk of death compared to a single agent treatment in advanced kidney cancer patients, according to first results of a phase 3 clinical trial.

UCLA study shows how interferon-gamma guides response to cancer immunotherapy
UCLA researchers shed light on how interferon-gamma (IFN-y) guides the treatment response in people with advanced melanoma who are treated with one of the leading immunotherapies -- immune checkpoint blockade.

checkmate 743 shows that dual immunotherapy, nivolumab + ipilimumab
The combination of first-line nivolumab and ipilimumab demonstrated an improvement of overall survival for patients with unresectable malignant pleural mesothelioma compared to platinum-based chemotherapy, according to research presented today at the International Association for the Study of Lung Cancer Virtual Presidential Symposium.

AI may help predict responses to non-small cell lung cancer systemic therapies
Using standard-of-care computed tomography (CT) scans in patients with advanced non-small cell lung cancer (NSCLC), researchers utilized artificial intelligence (AI) to train algorithms to predict tumor sensitivity to three systemic cancer therapies.

NCI-MATCH: Promising signal for nivolumab beyond colorectal cancer
The Journal of Clinical Oncology reports results for Arm Z1D of NCI-MATCH, investigating the activity of nivolumab in tumors with DNA mismatch repair deficiencies.

Experimental leukemia combination proves toxic for older, frail patients
About 32% of older, sicker patients enrolled on a leukemia clinical trial experienced serious side effects from a treatment that combined a chemotherapy and an immunotherapy drug, leading investigators to pause the trial and the US Food and Drug Administration to eventually pull the combination from the current study.

Immunotherapy in combination points to paradigm shift in the treatment of cervical cancer
Effective combination of nivolumab with ipilimumab for the treatment of patients with recurrent or metastatic cervical cancer, with or without prior systematic therapies, and irrespective of PD-L1 expression.

Combination immunotherapy drugs herald new hope for melanoma patients with long term survival rates
A combination of 2 immunotherapy drugs, ipilimumab and nivolumab, has stopped or reversed the progression of advanced melanoma for five years or more in one in two patients, according to a study led by The Royal Marsden NHS Foundation Trust.

Resistance to immune checkpoint blocker drug linked to metabolic imbalance
A metabolic imbalance in some cancer patients following treatment with a checkpoint inhibitor drug, nivolumab, is associated with resistance to the immunotherapy agent and shorter survival, report scientists from Dana-Farber Cancer Institute.

Read More: Nivolumab News and Nivolumab Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to