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Lung cancer is one of the most common causes of death worldwide, accounting for 1.8m fatalities in 20201. 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, accounting for 80-85% of all lung cancer cases. Treatment of NSCLC can be difficult, especially once 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 detected oncogenic driver in NSCLC.

Point mutations in KRAS codon12 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 they have remained elusive for over 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 and targeted therapy for NSCLC on May 28, 2021.

  • Sotorasib, under the brand name LUMAKRAS/LUMYKRAS, is approved in over 44 markets. Long-term findings from the CodeBreaK 100 trial (phase 1 and phase 2) were presented before the American Association for Cancer Research (AACR) on April 10, 2022. After a median follow-up of approximately two years, study participants lived a median of 6.3 months without their cancer worsening, and 12.5 months overall2.
  • 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, the drug delayed time to deterioration in patients’ health status, physical functioning, and cancer-related symptoms compared to docetaxel. These results were presented in ESMO Congress, 20223.
  • Sotorasib can also be used as a personalized therapy, especially for patients with G12C-mutated NSCLC.

Along with Sotorasib, Adagrasib is another KRAS inhibitor developed by researchers at Mirati Therapeutics.

  • Adagrasib showed promising results in pre-clinical testing and in phase I and Ib clinical trials.
  • In patients with previously treated KRAS G12C-mutated NSCLC, Adagrasib improved the median duration of response to 1.4 months and median overall survival to 11.1 months4.
  • In somein vitro studies, secondary mutations have been identified that confer resistance to KRAS inhibitors such as Sotorasib5.

Several drugs are in development targeting other gene mutations. Amivantamab and Mobocertinib for EFGR-mutant NSCLC, Tepotinib and Capmatinib for MET-mutant NSCLC, and Selpercatinib for RET fusion-positive NSCLC. All these drugs are in either phase I or phase II trials and show promising results.

The aim of any drug discovery and development program is to reduce the suffering of patients. The more the pharmaceutical industry understands the needs of patients, the more effective and efficient it will be in bringing valuable drugs to clinic. KRAS inhibitors could significantly improve the treatment of KRAS G12C-mutated NSCLC.

Cancer patients have many unmet medical and psychological needs. It’s essential they are given up-to-date information about the development and availability of effective treatments. Key opinion leaders (KOLs) play a critical role in disseminating that information.

  • KOLs interviewed by GlobalData expressed a preference for trying KRAS G12C inhibitors in combination with other agents to extend patients’ progression-free survival (PFS).
  • Grace Dy, MD, is chief of thoracic oncology at Roswell Park Comprehensive Cancer Center, specializing in lung cancer mesothelioma and thymic malignancies. At the annual meeting of the American Association for Cancer Research, She presented long-term data on Sotorasib from CodeBreak 100 trials and shared analysis of trial data on the performance of Sotorasib as a future treatment for
  • Joshua K. Sabari, MD, is an assistant professor in the department of medicine at the NYU Grossman School of Medicine. He participated in phase I and Ib trials of Adagrasib, and presented promising data about the drug’s efficacy in pretreated NSCLC patients6.

Reports of their work will help increase awareness among patients about the potential of Sotorasib and Adagrasib.

Role of KOLs in information flow from bench to clinic

KOLs serve as a link between researchers, healthcare professionals, and patients. They help improve the flow of information between these groups and amplify success stories about newly approved drugs and treatment modalities. In the case of Sotorasib and Adagrasib, experts who have participated in clinical trials or are made aware of these drugs will be able to effectively communicate their benefits to patients.

  • Thought leadership: Healthcare providers place great value on the opinions of prominent peers, researchers, and experts when recommending a treatment plan or drug to a patient.
  • Drug introductions: Healthcare professionals consume information published in journals or contribute directly by participating in clinical trials. The data they ingest helps them understand the advantages and challenges of a drug before prescribing it to a patient.
  • Prescription pattern: KOLs impact drug prescription patterns among fellow healthcare practitioners, health authority representatives, and patient communities.
  • Insights on new treatment: KOLs provide insight regarding new therapies and their efficacy on specific patient groups. For example, they can explain that Sotorasib will particularly benefit KRAS-mutated NSCLC patients.
  • Feedback on products: KOLs often share feedback on drugs by publishing research papers or speaking at conferences. Their opinions substantially affect the acceptance of new products or brands and influence patients’ decisions.

Excelra identifies KOLs who impact the communication of treatment benefits

At Excelra, we identify and map the most eminent KOLs in any given geography or domain. The KOLs we provide are outstanding in their therapeutic field. They support pharmaceutical companies in their go-to-market campaigns and help create awareness in healthcare professionals and patient communities.

We use advanced techno-human processes that effectively screen literature, websites, public sources, and conference records to create accurate KOL profiles that meet the specific requirements of our customers.

Supplying patients with effective treatments will improve their quality of life. That’s the primary objective of drug discovery and development programs. Successful and ambitious pharmaceutical companies know not to underestimate the role that optimized KOL data plays in achieving their goals.

References:

  1. https://www.who.int/news-room/fact-sheets/detail/cancer
  2. https://www.acs.org/content/dam/acsorg/events/drug-discovery/slides/2021-02-25-ddds1-sotorasib.pdf
  3. 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
  4. https://www.jto.org/article/S1556-0864(20)31003-0/fulltext#relatedArticles
  5. https://ascopubs.org/doi/full/10.1200/JCO.21.02752
  6. https://pubmed.ncbi.nlm.nih.gov/33971321/
  7. https://dailynews.ascopubs.org/do/10.1200/ADN.22.201038/full/