Cristiana Bernini

As explored in an abstract presented at the 2016 American Society of Clinical Oncology (ASCO) conference, the launch of Roche’s recently approved PD-1 immune checkpoint inhibitor Tecentriq (atezolizumab) will usher in a dramatic change in the treatment paradigm of metastatic bladder cancer, according to an analyst with research and consulting firm GlobalData.

The company’s most recent bladder cancer report states that the disease’s setting has been largely stagnant for almost 20 years, which largely explains why T atezolizumab has generated a considerable level of interest. In fact, on the heels of its approval as a second-line therapy following failure on platinum-based chemotherapy, there is already buzz about its potential expansion into the first-line setting.

GlobalData believes that the trial results presented at ASCO 2016 showed atezolizumab to be worthy of its praise. Of the 119 patients who were treated with atezolizumab once every three weeks in the drug’s Phase II, single-arm IMvigor 210 trial, overall response rate was reported to be 24% in all patients, with 7% being complete responses at a median follow-up of 14.4 months. Median overall survival was reported to be 14.8 months.

Cai Xuan, Ph.D., GlobalData’s Analyst covering Oncology and Hematology, explains: “The durable complete responses seen with Tecentriq treatment are extremely significant in advanced stage bladder cancer, as the disease is currently almost uniformly fatal. Though results from different trials should be compared with caution, it appears that despite a slightly lower overall response rate for Tecentriq than carboplatin-gemcitabine – the most commonly used frontline therapy – the patients who do respond to Tecentriq are gaining significant overall survival benefit compared to existing treatment options.

“Given the advanced age of most bladder cancer patients at diagnosis, it is estimated that up to 40% cannot receive cisplatin-based therapy due to renal impairment or other co-morbidities. According to GlobalData’s forecast, Tecentriq is set to reach sales of $270 million by 2017. If Roche can win a label expansion for the drug in the first-line setting, it can further solidify its expected dominance in the bladder cancer market as this would mean a larger target patient pool and potentially longer duration of therapy as compared with its current approval in the second line.

“This will depend on results from a larger randomized trial with the appropriate carboplatin-based chemotherapy comparator arm, and continued follow-up data from the patients who have confirmed complete responses in the current IMvigor 210 study”.

Dupilumab is first systemic therapy to show positive Phase 3 results in patients with moderate-to-severe atopic dermatitis, a serious, chronic inflammatory skin disease marked by widespread rash, itching and associated psychosocial comorbidities. In the studies, known as LIBERTY AD SOLO 1 and SOLO 2, treatment with dupilumab as monotherapy significantly improved measures of overall disease severity, skin clearing, itching, quality of life, and mental health.

A total of 1,379 adult patients with moderate-to-severe AD were enrolled in the identically-designed SOLO 1 and SOLO 2 trials. Patients were enrolled if they were not adequately controlled with topical medications, or if topical treatment was not medically advisable. All patients were assessed via the 5-point Investigator’s Global Assessment (IGA) scale, ranging from 0 (clear) to 4 (severe); entry criteria required a baseline score of 3 or 4. Patients were also assessed using the Eczema Area and Severity Index (EASI) and other measures. Patients were randomized into one of three treatment groups: dupilumab 300 mg subcutaneously once per week, dupilumab 300 mg subcutaneously every two weeks, or placebo for 16 weeks following an initial dupilumab loading dose of 600 mg subcutaneously, or placebo. For SOLO 1 and SOLO 2, respectively, 37 and 36% of patients who received dupilumab 300 mg weekly, and 38 and 36% of patients who received dupilumab 300 mg every two weeks, achieved clearing or near-clearing of skin lesions (IGA 0 or 1), compared to 10 and 8.5% with placebo (p less than 0.0001). This was the primary endpoint of the study in the U.S.

Moreover, for SOLO 1 and SOLO 2, respectively, the% improvement in EASI from baseline was 72 and 69% in patients who received the 300 mg weekly dose, and 72 and 67% for patients who received dupilumab 300 mg every two weeks, compared to 38 and 31% for placebo (p less than 0.0001). Last, for SOLO 1 and SOLO 2, respectively, 52.5 and 48% of patients who received dupilumab 300 mg weekly, and 51 and 44% of patients who received dupilumab 300 mg every two weeks, achieved EASI-75 compared to 15 and 12% with placebo (p less than 0.0001). This was the key secondary endpoint in the US for these studies and one of the primary endpoints in the EU.

For the 16-week treatment period, the overall rate of adverse events (65-73% dupilumab and 65-72% placebo) was comparable between the dupilumab groups and the placebo groups. The proportion of patients who completed the treatment period was 88-94% for dupilumab and 80.5-82% for placebo. The rate of serious adverse events was 1-3% for dupilumab and 5-6% for placebo. Serious and severe infections were also numerically higher in the placebo groups in both studies (0.5-1% dupilumab and 2-3% placebo). Adverse events that were noted to have a higher rate with dupilumab treatment across both studies included injection site reactions (10-20% dupilumab; 7-8% placebo), conjunctivitis (7-12% dupilumab; 2% placebo); approximately 26% of patients in both studies reported a history of allergic conjunctivitis at study entry. No patient discontinued therapy due to injection site reactions and only one patient discontinued therapy due to conjunctivitis.