NICE Recommends Mobocertinib for Rare, Aggressive Lung Cancer

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has issued final guidance recommending the use of mobocertinib (Exkivity) as a treatment option for patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations who have already received platinum-based chemotherapy.¹

No standard treatment is available to this population; as such, there is a clear unmet need for novel, effective options. This rare and aggressive disease is more commonly found in women, people from East Asian family backgrounds, and nonsmokers; it has also been associated with poorer outcomes vs NSCLC with other EGFR mutations.

The final guidance cautioned that mobocertinib, a first-in-class oral EGFR TKI, has not been evaluated in direct comparison with immunotherapies and docetaxel with or without nintedanib (Ofev) using real-world evidence; as such, cost-effectiveness estimates are uncertain. However, indirect comparisons suggest that mobocertinib increases overall survival (OS) and progression-free survival (PFS).

The list price for mobocertinib is £7,751 ($9,220.19) per pack of 112 capsules, each containing 40 mg of the active ingredient. Per usual for NICE approvals, drugmaker Takeda will offer the agent to the National Health Service at a discount.

“This is the first treatment approved by NICE that targets this specific gene mutation in people with advanced NSCLC,” Helen Knight, NICE interim director of medicines evaluation, stated in a news release. “I’m delighted that we have been able to recommend this innovative treatment for patients in England with this rare and aggressive form of lung cancer. The evidence shows it not only extends people’s lives but also extends how long people have before their cancer gets worse.”

The main support for mobocertinib comes from the platinum pretreated cohort (n = 114) of the Study AP32788-15-101 (NCT02716116), which is a single-arm, open-label, multicenter, phase 1/2 trial. Results published in November 2020 showed that treatment with mobocertinib resulted in a median PFS of 7.33 months (95% CI, 5.55-8.84) per investigator assessment and a median OS of 23.95 months (95% CI 14.55-28.81).² Mobocertinib also elicited a confirmed overall response rate of 28% (95% CI, 20%-37%) per independent review committee (IRC) assessment, with a median duration of response of 17.5 months (95% CI, 7.4-20.3).³

The FDA granted an accelerated approval to mobocertinib based on these data in September 2021.

To address the lack of a direct comparator, Takeda developed a blended comparator arm with real-world data collected from 93 patients treated in the United States and Germany. The indirect comparison showed that mobocertinib induced statistically significant improvements in OS (HR, 0.56, 95% CI 0.39-0.81) and PFS (HR, ratio 0.54 95% CI 0.36-0.82) compared with the blended comparator arm.²

NICE noted that EGFR TKIs have limited efficacy in people with exon 20 insertion mutations. The evidence review group explained that including an ineffective treatment option, the EGFR TKIs, in the blended comparator may have led to overestimating the comparative effectiveness of mobocertinib.

This is the nineteenth lung cancer drug recommended by NICE over the past 3 years, with a total of around 18,000 people eligible to receive these treatments. The treatment was licensed through Project Orbis, an international program launched to review and approve promising cancer drugs so that patients can access treatments faster.

“We are determined to drive ground-breaking treatments such as this into the hands of health and care professionals,” Knight said. “This treatment was licensed through Project Orbis, and we know how crucial collaborations with our colleagues in NHS England, MHRA and other organizations are to bringing innovative treatments to patients as rapidly as possible.”

References

1. Targeted treatment for rare form of aggressive lung cancer gets NICE approval. News release. National Institute for Health and Care Excellence. November 16, 2022. Accessed November 16, 2022. https://bit.ly/3Gm9MIr
2. Mobocertinib for treating EGFR exon 20 insertion mutation-positive advanced non-small-cell lung cancer after platinum-based chemotherapy: final appraisal document. National Institute for Health and Care Excellence; November 2022. Accessed November 16, 2022. https://bit.ly/3hO3FCI 
3. Takeda's EXKIVITY (mobocertinib) approved by US FDA as the first oral therapy specifically designed for patients with EGFR exon20 insertion+ NSCLC. News release. Takeda Pharmaceutical Company. September 15, 2021. Accessed November 16, 2022. https://bit.ly/2Xm3WSYiou9uu