Opdivo's (nivolumab) approvals were based on several studies.
The efficacy of Opdivo (nivolumab) on metastatic melanoma as single therapy emerged from two main studies in patients with advanced disease. The first study involving 418 previously untreated advanced melanoma patients found that patients treated with nivolumab survived longer than patients who received the cancer medicine dacarbazine: 73% of patients treated with nivolumab were alive at 12 months compared with 42% of patients given dacarbazine. The second study looked at 405 advanced melanoma patients whose disease worsened, despite previous treatment with a cancer medicine. In this study, around 32% (38 out of 120) of patients given nivolumab responded to treatment and had a reduction in their tumours compared with about 11% (5 out of 47) of patients given dacarbazine or a combination of carboplatin and paclitaxel6. In a phase 3 trial involving 120 patients with unresectable or metastatic melanoma, a reduction in tumour size was observed in 32 % of patients. The most notable observation was that this effect lasted in one-third of the patients (a durable response)7. An additional study involving 945 previously untreated advanced melanoma patients investigated nivolumab in combination with ipilimumab; nivolumab used alone and ipilimumab used alone. Patients who were given nivolumab plus ipilimumab lived for another 11.5 months without their disease worsening; patients who were given only nivolumab lived for another 6.9 months without their disease worsening. Patients given only ipilimumab lived for only 2.9 months without their disease worsening6.
The efficacy of nivolumab on NSCLC, both squamous and non-squamous, has been shown in comparison with another cancer medicine named docetaxel. For non-squamous NSCLC, one main study involved 582 patients whose disease had progressed despite previous treatments. The average survival with nivolumab was around 12.2 months, compared with 9.4 months with docetaxel. For squamous NSCLC, a study involving 272 patients showed that patients who were given nivolumab survived for around 9.2 months, compared with 6.0 months with patients given docetaxel. Supportive information was also provided from another study indicating that Opdivo could produce a response in patients with squamous NSCLC whose disease had progressed despite several previous treatments6.
The efficacy of nivolumab on renal carcinoma was based on an open-label randomised study of 821 patients with advanced renal cell carcinoma. Patients treated with nivolumab showed an overall survival of 25 months, as compared to patients treated with everolimus, with an overall survival 19.6 months6.
The efficacy of nivolumab on classical Hodgkin lymphoma (cHL) was based on two single-arm, multicentre trials of nivolumab in adults with relapsed or refractory cHL. Efficacy was evaluated in 95 patients previously treated with autologous HSCT and post-transplantation brentuximab vedotin. Single-agent nivolumab produced a 65 % objective response rate (ORR) (95% CI: 55%, 75%), with 58% partial remission and 7% complete remission. The median time-to-response was 2.1 months (range: 0.7 to 5.7 months). The estimated median duration of response (DOR) was 8.7 months8.
The efficacy of nivolumab on HNSCC was based on a study that enrolled 361 patients. It resulted that the overall survival was 7.5 months for patients treated with nivolumab and 5.1 months for patients treated with either cetuximab, methotrexate, or docetaxel9.
The efficacy of nivolumab on urothelial carcinoma was based on a study that enrolled 270 patients with platinum-refractory metastatic urothelial carcinoma. The objective response rate (ORR) was 19.6% while the complete response rate was 3%. The median progression-free survival (PFS) was 2.0 months and the median overall survival (OS) was 8.74 months10.
The efficacy of nivolumab on colorectal cancer was based on a study that enrolled 74 patients. Of these 32% (95% CI: 22–44; 24/74) responded to treatment with 2.7% (2/74) complete responses and 30% (22/74) partial responses. Among the 74 patients, 53 received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. In this group 28% of the patients responded to treatment with nivolumab, 1.9% had a complete response was (1/53) and 26% had a partial response (14/53). Among these responders, the median duration of response was not reached and it ranged between 2.8 to 22.1 months13.
The efficacy of nivolumab on hepatocellular carcinoma was based on a study that enrolled 154 patients who progressed on or were intolerant to sorafenib (a chemotherapy). According to the Response Evaluation Criteria In Solid Tumors (RECIST) 14.3% (95% CI: 9.2, 20.8) of the patients responded to the treatment with 1.9% complete responses. The duration of response ranged from 3.2 months to over 38.2 months, with 55% of those patients having responses of 12 months or longer1.