Key opinion leaders in lung cancer treatment play a critical role in accelerating the delivery of emerging novel therapies to patients. Lung cancer is one of the most common causes of death worldwide, accounting for 1.8 million fatalities in 2020. There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is the most common form, accounting for 80–85% of all lung cancer cases.
Treatment of NSCLC can be difficult, especially once the cancer has metastasized. Challenges include gene mutations, drug resistance, and tumor heterogeneity. Acquired mutations, which occur following cell damage, are responsible for most cases of lung cancer. Following that are germline mutations in oncogenes such as EGFR, BRAF, MET, HER2, and KRAS. The KRAS oncogene is the most frequently detected oncogenic driver in NSCLC.
KRAS mutations and targeted NSCLC therapies
Point mutations in KRAS codon 12 are present in up to 80% of KRAS-mutant malignancies. The development of therapeutically effective inhibitors could be beneficial for patients suffering from G12C-mutated NSCLC, but such treatments remained elusive for more than 30 years. In search of KRAS inhibitors, researchers at Amgen identified a novel scaffold while screening libraries of cysteine-reactive compounds. The lead compound was named Sotorasib.
No effective treatments were available that counteracted G12C mutant KRAS proteins until the FDA approved Sotorasib as the first targeted therapy for NSCLC on May 28, 2021. This milestone highlights how key opinion leaders in lung cancer treatment help translate scientific breakthroughs into real-world oncology practice.
Clinical evidence supporting KRAS G12C inhibitors
Sotorasib, marketed as LUMAKRAS/LUMYKRAS, is approved in over 44 markets. Long-term findings from the CodeBreaK 100 trial (phase I and II) were presented at the American Association for Cancer Research (AACR) meeting on April 10, 2022. After a median follow-up of approximately two years, study participants experienced a median progression-free survival of 6.3 months and a median overall survival of 12.5 months.
The drug demonstrated a favorable benefit-risk profile with rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic NSCLC. In phase III trials, Sotorasib delayed deterioration in patients’ health status, physical functioning, and cancer-related symptoms compared with docetaxel, with results presented at the ESMO Congress 2022.
Sotorasib can also be used as a personalized therapy, particularly for patients with G12C-mutated NSCLC. Alongside Sotorasib, Adagrasib is another KRAS inhibitor developed by researchers at Mirati Therapeutics.
Emerging treatments and resistance mechanisms
Adagrasib demonstrated promising results in pre-clinical studies and phase I/Ib clinical trials. In patients with previously treated KRAS G12C-mutated NSCLC, Adagrasib improved median duration of response to 1.4 months and median overall survival to 11.1 months. However, some in vitro studies have identified secondary mutations that confer resistance to KRAS inhibitors such as Sotorasib.
Several additional therapies targeting other gene mutations are in development, including Amivantamab and Mobocertinib for EGFR-mutant NSCLC, Tepotinib and Capmatinib for MET-mutant NSCLC, and Selpercatinib for RET fusion-positive NSCLC. These therapies are currently in phase I or phase II trials and show encouraging results.
Why key opinion leaders in lung cancer treatment matter
The ultimate aim of any drug discovery and development program is to reduce patient suffering. Cancer patients have many unmet medical and psychological needs, making it essential they receive up-to-date information on treatment availability. Key opinion leaders in lung cancer treatment play a vital role in disseminating credible, evidence-based information to both clinicians and patients.
KOLs interviewed by GlobalData expressed a preference for using KRAS G12C inhibitors in combination regimens to extend progression-free survival. Grace Dy, MD, Chief of Thoracic Oncology at Roswell Park Comprehensive Cancer Center, presented long-term Sotorasib data from the CodeBreaK 100 trials at AACR. Joshua K. Sabari, MD, Assistant Professor at NYU Grossman School of Medicine, participated in Adagrasib trials and shared promising efficacy data in pretreated NSCLC patients.
Role of KOLs in information fow from bench to clinic
Key opinion leaders in lung cancer treatment serve as a bridge between researchers, healthcare professionals, and patient communities. Their involvement improves the flow of information from bench to clinic and accelerates adoption of newly approved therapies.
- Thought leadership: Influencing treatment decisions through expert clinical insight
- Drug introductions: Educating peers through journals and clinical trial participation
- Prescription patterns: Shaping oncology prescribing behavior
- Insights on new treatments: Identifying patients most likely to benefit
- Product feedback: Publishing data and presenting real-world experiences
Excelra’s expertise in mapping key opinion leaders in lung cancer treatment
At Excelra, we identify and map the most eminent key opinion leaders in lung cancer treatment across geographies and therapeutic domains. Our experts use advanced techno-human curation processes to screen scientific literature, public sources, clinical trial records, and conference proceedings.
Our KOL identification and mapping services, combined with clinical data services and data science solutions, support pharmaceutical companies in effective go-to-market strategies.
By enabling accurate, up-to-date KOL intelligence, Excelra helps accelerate patient access to innovative lung cancer therapies and supports improved outcomes across the oncology care continuum.
References:
- https://www.who.int/news-room/fact-sheets/detail/cancer
- https://www.acs.org/content/dam/acsorg/events/drug-discovery/slides/2021-02-25-ddds1-sotorasib.pdf
- https://www.aacr.org/about-the-aacr/newsroom/news-releases/kras-g12c-inhibitor-sotorasib-may-offer-long-term-clinical-benefit-in-patients-with-non-small-cell-lung-cancer
- https://www.jto.org/article/S1556-0864(20)31003-0/fulltext#relatedArticles
- https://ascopubs.org/doi/full/10.1200/JCO.21.02752
- https://pubmed.ncbi.nlm.nih.gov/33971321/
- https://dailynews.ascopubs.org/do/10.1200/ADN.22.201038/full/
