Reducing Standard Dosage of Immunotherapy Drug Has No Effect on Lung Cancer Patients

A new study of another immunotherapy drug, Nivolumab (trade name Opdivo), has found that small-dose treatment of lung cancer patients was as effective as normal-dose treatment. Inevitably, small-dose treatment comes at a much reduced cost.[i]

Nivolumab is an immunotherapy cancer treatment, meaning that it activates the body’s own immune system, allowing it to destroy cancer cells.  This is achieved by blocking the immune cells from attacking the cancer cells. As discussed in the previous article, Keytruda has shown promise in the treatment of mesothelioma patients. As a result, schedules of loss in living mesothelioma claims have begun calculating future care damages with Keytruda therapy in mind.

The New Study

The purpose of the latest Nivolumab study was to evaluate the efficacy of low-dose treatment compared to standard-dose treatment.  In the USA, Nivolumab is approved for the treatment of non-small cell lung cancer, with a dose of 3 milligrams for each kilogram of body weight (3 mg/kg), or a fixed dose of 240 mg every 2 weeks. 

29 participants in the study were given the standard treatment of 3 mg/kg every 2 weeks, while the 18 remaining participants were given a lower, fixed dose of either 20 or 100 mg every 3 weeks.

The researchers investigated survival time without disease progression and overall patient survival time. The average progression-free survival and overall survival times were longer among patients who were administered a smaller dose of Nivolumab.

These averages were based on a small number of lung cancer patients. As such, it is likely that any difference in survival time is due to chance alone.

However, the study results clearly show that those treated with smaller doses of Nivolumab did not face shorter survival times.  The authors of the study were able to conclude that low-dose Nivolumab can be just as effective as the standard-dose and encouraged further study of low-dose efficacy.

Other Studies of Nivolumab as Mesothelioma Treatment

There are several studies underway into the effectiveness of Nivolumab treatment among mesothelioma patients.[ii] 

Japanese researchers, for example, are conducting a phase II trial of Nivolumab in combination with first-line chemotherapy treatment.

Elsewhere, Dutch researchers have found that Nivolumab had ‘meaningful clinical efficacy’ as a treatment for mesothelioma.[iii] 8 out of 34 patients had a partial response after 12 weeks of treatment, while the disease was stabilised in another patient. The disease control rate (tumours either shrunk or did not grow) was calculated at 47%.

Another study found that Nivolumab treatment in isolation, or a combination treatment of Nivolumab plus ipilimumab, may provide an alternative for mesothelioma patients who have previously received chemotherapy.[iv]

Ipilimumab, another immunotherapy drug, targets a protein known as CTLA-4. 

After 12 weeks, researchers found that 125 patients receiving Nivolumab had a disease control rate of 42.6%. Meanwhile, patients receiving Nivolumab and ipilimumab together had a disease control rate of 51.9%.

More recent results from this trial, presented in September 2017, produced a 1 year survival rate of 51% in the Nivolumab group and 58% in the combination group.[v] 

Median overall survival was 13.6 months in the Nivolumab group, and has not yet been reached in the combination group, meaning that more than 50% of this group are still alive.

Pembrolizumab (Keytruda) Dosage

In the KEYNOTE-010 study of lung cancer patients, published in 2016, there was no difference in efficacy when the patients were administered doses of 2 and 10 mg/kg.[vi]

As a result of these findings, the Food and Drug Administration (FDA) established that higher doses were unnecessary and approved a lower dose of 2 mg/kg (this was later adapted to the standard dosage of 200 mg). 

Approved Keytruda therapy therefore prescribes a dose of 200 mg every 2 to 3 weeks (usually every 3)[vii].  This is the equivalent of 2.7 mg/kg for a 75 kg adult.


If it becomes common practice for damages for future care in mesothelioma claims to include Keytruda therapy, it is possible that claims for alternative therapies, which show consistent promise in clinical trials, may also appear on schedules of loss.

The high unit cost of immunotherapy treatments translates to a significant cost per dose. If a mesothelioma claimant is treated with Nivolumab, in light of the recent study, a lower, cheaper dose may be the appropriate course.



[i] Yoo, S. H. et al. Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity. ESMO Open 3, e000332 (2018). And (Accessed 17 August 2018)

[ii] Opdivo for Malignant Mesothelioma: Could a Lower Dose Work? Surviving Mesothelioma 11 August 2018. (Accessed 20 August 2018)

[iii] Quispel-Janssen, J. et al. Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma. J Thorac Oncol (2018). doi:10.1016/j.jtho.2018.05.038 (Accessed 20 August 2018)

[iv] Scherpereel, A. et al. Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Results of the IFCT-1501 MAPS2 randomized phase II trial. JCO 35, LBA8507-LBA8507 (2017). (Acessed 4 June 2018)

[v] ESMO 2017 Press Release: Combination Immunotherapy in Second/third Line Extends Mesothelioma Survival to 15 Months. ESMO, 10 September 2017. (Accessed 4 June 2018)

[vi] Herbst, R. S. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet 387, 1540–1550 (2016). (Accessed 20 August 2018)

[vii] Dosing with Keytruda. (Accessed 20 August 2018)