Nivolumab improves the proportion of lung cancer patients alive after more than a year

ECC2015 Press release:

Vienna, Austria: Patients with a type of lung cancer called non-squamous non-small cell lung cancer (non-SQ NSCLC) have limited treatment options and a dismal prognosis once their disease has advanced and initial treatment with platinum-based chemotherapy has failed. Second-line treatment is usually with another chemotherapy drug, such as docetaxel or pemetrexed.

Recent results have shown that the drug, nivolumab, improves survival for these patients and now updated results from the CheckMate 057 phase III clinical trial, to be reported at the 2015 European Cancer Congress[1] today (Monday) with simultaneous publication of the study results in the New England Journal of Medicine[2], show that nivolumab continues to show an overall survival benefit compared to docetaxel. Among patients randomised to receive nivolumab, significantly more were alive at 12 months compared to those treated with docetaxel – 51% versus 39% respectively – and a difference in survival remains at 18 months – 39% for nivolumab versus 23% for docetaxel[3].

This improvement in survival was observed for all patients included in the trial, but nivolumab was more effective in patients whose tumours expressed a protein called programmed death ligand 1 (PD-L1), which plays a role in the immune system’s ability to recognise and attack tumours and has been correlated with response to immune checkpoint inhibitors such as nivolumab[4].

The researchers found there was a difference in the objective response rate (ORR) between patients with tumours expressing different levels of PD-L1 (ORR is the proportion of patients who experience a reduction in tumour size for a minimum time period). However, PD-L1 made little difference to the duration of the response in the patients on nivolumab. There was an ORR of 31% among patients with tumours expressing PD-L1 in at least one percent of cells, compared to nine percent in patients with tumours with PD-L1 expressed in less than one percent of cells. However, the difference in the median duration of the response was 16 months versus 18.3 months respectively, which was not statistically significant. Among patients receiving docetaxel the duration of response was 5.6 months, regardless of PD-L1 expression.

Leora Horn, Associate Professor of Medicine at the Vanderbilt Ingram Cancer Center, Nashville, USA, will tell the Congress: “The results from this trial show that for patients with non-squamous non-small cell lung cancer who have progressed on prior platinum-based chemotherapy, nivolumab is a good treatment option showing durable benefit with fewer side effects regardless of PD-L1 tests results compared to treatment with docetaxel.”

Patients treated with nivolumab suffered fewer significant treatment-related adverse events (grades 3-4) compared to patients on docetaxel: 10% and 54% respectively. Data presented at the Congress show that this was regardless of PD-L1 expression. There were 13% and 53% treatment-related grade 3-4 side effects for nivolumab and docetaxel respectively in patients with tumours that stained positive for PD-L1 in at least one percent of cells, compared to 8% and 58% for nivolumab and docetaxel respectively in patients with tumours that stained positive for PD-L1 in less than one percent of cells. Moreover, patient-reported outcomes, as measured by the Lung Cancer Symptom Scale, showed a better quality of life with slower deterioration for patients treated with nivolumab compared to docetaxel.

In the international clinical trial, 292 patients were randomised to receive treatment with nivolumab at a dose of 3 mg/kg administered intravenously every two weeks and 290 received docetaxel at a dose of 75 mg/m2 intravenously every three weeks. Treatment continued until the cancer progressed or patients discontinued due to toxic side effects.

“Similar to prior studies, response rates to nivolumab were higher in current and former smokers compared to never smokers: 22% and 9% compared to 11% and 15% for docetaxel respectively. Responses were observed in patients with and without cancer-driving mutations in the epidermal growth factor receptor (EGFR): 11% and 18% respectively with nivolumab compared to 16% and 9% respectively with docetaxel,” said Professor Horn.

Professor Peter Naredi, the ECCO scientific co-chair of the Congress, who was not involved in the research, commented: “At the European Cancer Congress this year we are fortunate to have many presentations of randomised phase III trials that will most likely change the stage for treatment of cancer. Professor Horn and a group of collaborators in Europe and the US now show that nivolumab, a PD-1 immune checkpoint inhibitor, is also effective in non-squamous non-small cell lung cancer. This will be important for all those patients for whom prior treatment with chemotherapy has failed.”


Abstract no: 3010. “Phase 3, randomized trial (CheckMate 057) of nivolumab vs docetaxel in advanced non-squamous non-small cell lung cancer: Subgroup analyses and patient reported outcomes”. Lung cancer – metastatic disease, proffered paper session, 09.00-11.10 hrs (CEST), Monday 28 September, Strauss Hall (presenting at 10.20 hrs).


[1] The European Cancer Congress is the 18th congress of the European CanCer Organisation (ECCO) and the 40th congress of the European Society for Medical Oncology (ESMO).
[2] “Nivolumab versus docetaxel in advanced non-squamous non-small cell lung cancer”, by Hossein Borghaei et al. doi: 10.1056/NEJMoa1507643. Published online:
[3] More details on survival data will be given by Professor Horn in her presentation at ECC2015.
[4] Nivolumab is an inhibitor of programmed cell death protein 1 (PD-1). In cancer cells PD-1 binds to the molecule PD-L1 and inhibits the body’s immune response to a tumour. By blocking the interaction between PD-1 and PD-L1 by using anti-PD1 therapy, such as nivolumab, the immune system recognises and attack tumours.
[5] Bristol-Myers Squibb sponsored the trial.



Drug combination improves progression-free survival in melanoma patients regardless of genetic status, age and spread of disease

ECC2015 Press release:

Vienna, Austria: Patients with advanced melanoma skin cancer survive for longer without their disease progressing if they have been treated with a combination of two drugs, nivolumab and ipilimumab, than with either of these drugs alone. New results show that these patients also do better regardless of their age, stage of disease and whether or not they have a cancer-driving mutation in the BRAF gene.

Dr James Larkin, a Consultant Medical Oncologist at The Royal Marsden, London, UK, told the 2015 European Cancer Congress[1], that results from the CheckMate 067 phase III clinical trial had already shown that the combination of the two drugs, which target two different pathways that regulate the immune system, improved the progression-free survival in patients with melanoma who had not received any other treatment. However, until now it was not known whether this remained the case when the results were analysed according to genetic status, age and how advanced was their disease.

Nivolumab is an inhibitor of the programmed cell death protein 1 (known as PD-1), which functions as an immune checkpoint, playing an important role in the immune system. Ipilimumab inhibits the CTLA-4 checkpoint, which also plays a role in the immune system[2].

Dr Larkin said: “Results from our large analysis of pre-defined sub-groups of patients with advanced melanoma provide evidence that suggests the combination of the two drugs consistently improves progression-free survival across a range of sub-groups, including patients with poor prognostic factors, when compared with either nivolumab or ipilimumab alone.”

Out of a total of 945 patients in 20 different countries[3] who were randomised to receive the combination therapy or one of the drugs alone, those on the combination therapy survived for an average of 11.5 months without their disease progressing, compared, to 6.9 months for patients on nivolumab alone and 2.9 months for those on ipilimumab alone.

When the researchers looked at progression-free survival times among patients with and without the V600 type of mutation of the BRAF gene, the average for patients taking both drugs without the mutation was 11.2 months, and it was 11.7 months for those with the mutation. This compared with 7.9 months and 5.6 months respectively for patients on nivolumab alone and 2.8 months and four months respectively for those on ipilimumab alone.

“These results provide evidence that the efficacy of the combination therapy is similar whether or not the tumours harbour BRAF mutations. This has important practical implications for clinicians treating patients with melanoma,” said Dr Larkin.

The same pattern was seen when the researchers looked at groups of patients according to the extent of the spread of the disease to other parts of the body (metastases), and whether the patients were aged less that 65, between 65 and 75, and 75 and older (older patients can often be less able to cope with the side effects of treatments).

Among patients with metastatic melanomas with the worst prognosis (stage M1c), the average progression-free survival times were 8.5 months for the combination treatment, 5.4 months for nivolumab alone and 2.8 months for ipilimumab alone.

Patients younger than 65 years, had average progression-free survival times of 11.7 months (combination), 5.5 months (nivolumab) and 2.8 months (ipilimumab), while the 262 patients aged between 65 and 75 had average progression-free survival times of 11.1 months, 12.7 months and 2.9 months respectively. For those aged 75 and over (118 patients), the average progression-free survival time for those on the combination treatment could not be calculated as the patients’ disease had not progressed yet; it was 5.3 months for those on nivolumab alone and four months for those on ipilimumab alone.

Dr Larkin said: “The sub-groups included in these analyses are those of particular interest to melanoma clinicians, such as patients aged 75 and over. We believe that the data will give confidence to patients and their healthcare providers that the combination of nivolumab and ipilimumab will be effective regardless of advanced age, the presence of a BRAF mutation, or poor prognostic factors.”

Overall, significant (grade 3-4) side effects related to treatment occurred in 55%, 16% and 27% of patients in the combination, nivolumab and ipilimumab groups respectively. A similar pattern was seen in the sub-groups of patients; for instance, in patients aged 75 and over, significant side effects occurred in 48%, 21% and 36% respectively, and in patients with stage M1c disease, they occurred in 54%, 14% and 25% respectively.

The most common side effects were those that related to the way the drugs affect the functioning of the immune system, such as diarrhoea, colitis (inflammation of the lining of the colon) and raised levels of alanine aminotransferase (an enzyme, raised levels of which can indicate liver damage).

The CheckMate 067 trial started in May 2013, recruitment of patients ceased in 2014, and the next significant milestone will be when the researchers report results on overall survival.

Professor Peter Naredi, the ECCO scientific co-chair of the Congress, who was not involved in the research, commented: “Although the CheckMate 067 study has already reported that a combination of two checkpoint inhibitors, nivolumab and ipilimumab, is superior to either drug alone, the results presented here in Vienna have important clinical implications. These drugs come with a substantial frequency of adverse effects for the patients and it is important to spare patients who will not benefit from the treatment. What Dr Larkin and co-authors show is that bad prognostic indicators, such as BRAF mutations, metastatic pattern or increased age, do not negatively influence progression-free survival. Therefore, more patients can be considered for treatment, and tolerance to the treatment becomes a more important factor.”


Abstract no: 3303. “Efficacy and safety in key patient subgroups of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naïve patients with advanced melanoma (MEL) (CheckMate 067)”. Melanoma and skin cancer II proffered paper session, Monday 28 September, 09.00-10.50 hrs (CEST), Hall C3, (presenting at 09.55 hrs).


[1] The European Cancer Congress is the 18th congress of the European CanCer Organisation (ECCO) and the 40th congress of the European Society for Medical Oncology (ESMO).
[2] CTLA-4 stands for cytotoxic T-lymphocyte antigen 4.
[3] The study was conducted at 137 centres in 20 countries in Australia, Europe, Israel, New Zealand, and North America. The authors of the current study represent nine of these countries: Australia, Canada, Europe (Belgium, France, Germany, Italy, and the UK), Israel, and the United States. 
[4] Bristol-Myers Squibb funded the CheckMate 067 trial and these analyses.