Low-Dose Nivolumab Shows Responses in Retrospective Nepal Cancer Cohort

In a retrospective study of 31 patients with advanced cancers treated at a single center in Nepal, low-dose nivolumab was associated with an overall response rate of 51.6% and a disease control rate of 67.7%. The cohort received 20 or 40 milligrams every three weeks after showing limited response to conventional treatment and being unable to afford the standard regimen. Sixteen of the 31 patients, or 51.6%, achieved a complete or partial response, while five had stable disease.

These observations suggest clinical activity across several tumor types, but the small, uncontrolled cohort, heterogeneous treatments and limited follow-up prevent firm conclusions about the effectiveness of reduced doses relative to standard dosing. Researchers analyzed patients treated between March 2022 and March 2024. The population included gastrointestinal, lung, head-and-neck, gynecologic, skin cancers and Hodgkin lymphoma.

The median age was 51 years, with a range of 28 to 87 years. Eleven patients had an Eastern Cooperative Oncology Group performance status of 0 and 12 had a status of 1, while five had a status of 2 and three had a status of 3. Eight patients, representing 25.8% of the cohort, received nivolumab without previous systemic therapy; the others had received one or more prior lines of treatment.

Five patients also received cytotoxic chemotherapy alongside nivolumab, introducing heterogeneity that complicates attribution of responses or other outcomes to the reduced-dose antibody alone. Investigators selected either a 20- or 40-milligram dose according to the treating physician’s preference and the patient’s financial circumstances. The 20-milligram dose was administered to 20 patients, or 64.5% of the cohort, while 11 patients, or 35.5%, received 40 milligrams.

Patients were explicitly informed that nivolumab was being used off label at a reduced dose and that the supporting evidence was limited. Because the hospital pharmacy stocked nivolumab in 40-milligram vials, the pharmacy implemented vial sharing. Treatment continued until disease progression, unacceptable toxicity or financial hardship prevented further therapy.

Patients who received only one dose or whose records were incomplete were excluded from the analysis. Response was evaluated using the available radiological imaging, which included ultrasonography, computed tomography, magnetic resonance imaging or positron-emission tomography combined with computed tomography. Solid-tumor responses were assessed under Response Evaluation Criteria in Solid Tumors version 1.1, while the patient with Hodgkin lymphoma was assessed under the Lugano classification.

Progression was recorded only when imaging showed unequivocal tumor enlargement or the appearance of new lesions consistent with malignant progression. Adverse events documented in routine medical records were retrospectively abstracted and graded with version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. Grade 1 events were not systematically recorded during outpatient visits, so the safety analysis was restricted to reliably documented events.

Patients received a median of nine nivolumab cycles, with a range of two to 20, over a median treatment duration of 5.7 months, ranging from 0.7 to 17.1 months. The best documented response was a complete response in four patients, or 12.9%, and a partial response in 12, or 38.7%. Stable disease occurred in five patients, or 16.1%; seven patients had progressive disease, and three were not evaluated for their best response.

Among all 31 patients, the overall response rate was 51.6%, with a 95% confidence interval of 33.1% to 69.8%, and the disease control rate was 67.7%, with a 95% confidence interval of 48.6% to 83.3%. Among the 28 evaluable patients, the corresponding rates were 57.1% and 75%, with 95% confidence intervals of 37.2% to 75.5% and 55.1% to 89.3%, respectively. Median follow-up was 8.6 months, with a 95% confidence interval of 7.1 to 12.9 months.

Median progression-free survival, measured from the first nivolumab administration until progression or death from any cause, was 8.8 months, with a 95% confidence interval of 6.6 months to not reached. The estimated six-month progression-free survival rate was 66.1%, with a 95% confidence interval of 50.9% to 80.9%. Median overall survival was 14.8 months, with a 95% confidence interval of 11.1 months to not reached.

The median duration of response among patients who achieved a complete or partial response was four months, with a range of 0.8 to 8.2 months. At the end of the study period, three patients were alive without disease, 22 were alive with disease and six had died. Grade 2 or 3 adverse events were uncommon in the available records.

Two patients developed arthralgia, one at grade 2 and one at grade 3. Two patients had grade 2 diarrhea, and one had a grade 2 pericardial effusion. No additional grade 2 or higher events were documented, and no grade 4 events were recorded.

The recorded safety signal was therefore limited, although incomplete capture of grade 1 events, the retrospective design and short follow-up mean that the findings cannot establish that reduced doses have the same safety profile as standard treatment. Financial hardship remained a problem even under the lower-cost regimen: four patients stopped treatment, including one in complete remission and one with a partial response. The results were broadly consistent with several earlier studies discussed by the researchers.

One report found comparable disease control among low, weight-based and conventional doses of immune checkpoint inhibitors across various cancers, while another reported similar response rates with 40-milligram and conventional-dose nivolumab in advanced cancers. In nonsmall-cell lung cancer, a study found no significant difference in response rate, progression-free survival or overall survival between low doses of 20 or 100 milligrams and standard-dose nivolumab. Another study in hepatocellular carcinoma reported no statistical difference in disease control between 20 and 100 milligrams.

A phase III trial across various tumors reported a median overall survival of 5.88 months with 20-milligram nivolumab compared with 4.7 months for standard chemotherapy, along with one-year survival rates of 27.3% and 16.9%, respectively. Another study in head-and-neck cancer reported improved one-year overall survival with 20-milligram nivolumab compared with standard chemotherapy. These are indirect comparisons because the present study involved neither randomized allocation nor a standard-dose nivolumab control group.

Economically, the study regimen used 20 to 40 milligrams every three weeks, compared with approved nivolumab schedules of 240 milligrams every two weeks or 480 milligrams every four weeks. At a reported cost of approximately 7 dollars per milligram, investigators estimated savings of 80% to 90% relative to standard dosing. Vial sharing was used to make use of partially filled vials, and the availability of biosimilar nivolumab was described as another means of reducing treatment costs.

The researchers also cited pharmacokinetic findings suggesting that therapeutic drug monitoring could help investigate more individualized doses, schedules or frequencies, given nivolumab’s reported half-life of about 25 days. Such cost estimates and exposure measurements do not establish therapeutic equivalence: the present cohort lacked a randomized comparison with approved dosing, and clinical responses observed alongside lower expenditure cannot show that reduced doses produce the same benefit. It was retrospective, conducted at one cancer center and included only 31 patients without a control group.

Selection bias is possible because treatment was chosen in the context of each patient’s finances and the treating physician’s preferences. The cancer types, prior treatment histories and performance statuses varied, five patients received concomitant chemotherapy, PD-L1 status was known for only six patients and three were not evaluable for response. Follow-up was too short to characterize long-term durability, late toxicity or survival reliably.

The findings are therefore hypothesis-generating rather than evidence that 20- or 40-milligram nivolumab can replace approved regimens. Larger controlled studies are needed to confirm whether lower doses can reproduce response and survival outcomes, define an appropriate dose range and establish safety more precisely.

Subject of Research: Real-world outcomes of reduced-dose nivolumab in patients with advanced cancer

Article Title: Low‐Dose Nivolumab in Various Cancers: A Real‐World Exploratory Analysis in Resource‐Constrained Settings

Article References: Pandit, S., Sapkota, S., Adhikari, A., Bhandari, J., Shrestha, S., Jha, R., Prasai, G., & Jha, A. K. (2026). Low‐Dose Nivolumab in Various Cancers: A Real‐World Exploratory Analysis in Resource‐Constrained Settings. Cancer Reports, 9(10), Article e70713. https://doi.org/10.1002/cnr2.70713

Image Credits: AI Generated

DOI: 10.1002/cnr2.70713

Keywords: low-dose nivolumab, cancer immunotherapy, PD-1 inhibitor, retrospective cohort, advanced cancer, dose optimization, treatment affordability, Nepal, overall response rate, progression-free survival, Dose, Nivolumab