The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial

FDA Approves New Drug For Advanced Lung Cancer

Dec. 19, 2024 – The FDA has approved a new drug called ensartinib for adults with a type of lung cancer called ALK-positive non-small-cell lung cancer (NSCLC). Sold under the brand name Ensacove, this drug is now a first-choice treatment for people with this type of cancer. It is for patients whose cancer has either grown nearby or spread to other parts of the body and who haven't been treated with an ALK-blocking drug before.

ALK-positive NSCLC is frequently diagnosed in younger people with little to no history of smoking. It arises from certain changes in the ALK gene that produce abnormal fusion proteins, promoting growth and spread of cancer cells. ALK-positive NSCLC makes up about 3% to 11% of all lung cancer cases and is often more aggressive, with a higher chance of coming back after treatment and worse results. This highlights the need for specific drugs that can stop the effects of these abnormal fusion proteins.

Ensartinib is a new second-generation ALK inhibitor that blocks the activity of faulty ALK proteins by preventing their access to energy molecules within cancer cells. In this way, ensartinib disrupts the signals that help cancer cells grow, reduces tumor growth, and leads to cancer cell death. Developed jointly by Xcovery and Betta Pharmaceuticals, this once-daily oral drug is designed to overcome the shortcomings of current therapies and improve outcomes in patients with ALK-positive NSCLC. 

The approval was based on promising results from a clinical trial that assessed the effectiveness of ensartinib versus crizotinib (a first-generation ALK inhibitor) in 290 patients with advanced ALK-positive NSCLC who had not previously received any ALK inhibitor therapy. Patients were randomly assigned to receive either ensartinib or crizotinib. Results showed that ensartinib significantly improved progression-free survival, with patients living for about 25.8 months on average without their cancer worsening; in contrast, those taking crizotinib lived for about 12.7 months on average without cancer progression. However, no significant difference in overall survival was noted between the two groups of patients. 

Common side effects included cough, itching, rash, muscle pain, constipation, nausea, swelling, fever, and tiredness.

Dispelling Common Myths Surrounding Lung Cancer

As an oncologist, I see a concerning trend among the patients and the community —a tangle of myths and misunderstandings about lung cancer. These misconceptions can distort the reality of the disease, making people less likely to take proactive steps. Lung cancer remains one of the deadliest cancers, claiming hundreds of thousands of lives each year, and is unfortunately misunderstood in ways that hinder timely diagnosis and treatment. According to recent statistics from National Cancer Registry, India alone anticipates over 100,000 new cases of lung cancer in the next five years. According to GLOBOCAN 2020 data, lung cancer in India accounted for 85,221 new cases and 70,264 deaths. It is the second most common cancer in India by incidence and the leading cause of cancer-related deaths in the country. The age-standardized incidence rate (ASIR) is 7.3 per 100,000, while the age-standardized mortality rate (ASMR) is 5.3 per 100,000. Lung cancer is more prevalent in men due to higher smoking rates, although non-smokers, especially women, are also increasingly affected by environmental pollution and genetic factors. Early detection and effective treatment remain critical challenges. Correcting misconceptions around lung cancer can revolutionise lung cancer awareness, early detection and enhanced treatment, leading to drastically improved outcomes.Some of the most pervasive myths about lung cancer include the following:Myth: Smoking is the only risk factor.Fact: While smoking remains a leading cause, approximately 30% of lung cancers occur in never smokers. This is thought to be as a result of increasing rates of pollution, environmental carcinogen, radon, diesel fumes, second hand smoke, asbestos or silica exposure at work as occupational hazard, and even genetic predisposition as a part of cancers that run in families. In a recent study Dr. Charles Swanton led a study published in Nature (2019) that explored the link between air pollution and a type fo lung cancer seen in non-smokers called EGFR-positive lung cancer. The research found that long-term exposure to PM2.5 in the environment was significantly associated with EGFR mutation positive lung cancer in non-smokers. This study suggested that pollution may act as a carcinogen, contributing to genetic mutations in the epidermal growth factor receptor (EGFR), a key driver in non-small cell lung cancer (NSCLC). Swanton's findings underscore the growing role of environmental factors in the development of lung cancer, even without smoking. [Nature, 2019]. Myth: All lung cancers are the same.Fact: Lung cancer is not a single disease; traditionally it included two main types—non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, now there is a clear demarcation between smokers lung cancer and non-smokers lung cancer. Non-smokers lung cancers mostly harbour a driver mutation that should be treated with targeted therapy for transformative outcomes. Smokers lung cancer may better respond to immunotherapy. Lung cancer is biologically classified into many different genomic subtyoes and understanding which type of lung cancer a person has and strategizing the treatment based on that has revolutionized the management of lung cancer and transformed outcomes.Myth: A lung cancer diagnosis is always terminal.Fact: Globally, around 70-75% of lung cancer cases are diagnosed at an advanced stage, limiting survival rates. In India, the situation is similar, with 60-70% of lung cancer cases being detected at advanced stages, primarily due to delayed diagnosis, lack of screening, and limited awareness. Novel therapies, including immunotherapy and targeted therapy, have changed the outlook for many patients globally and also in India. The idea is to get to a comprehensive cancer center and seek genomic testing to classify the type of lung cancer in order to strategize the best treatment at the fastest possible pace, to achieve best outcomes.Myth: Lung cancer cannot be treated effectively.Fact: Thanks to advances in surgery, chemotherapy, radiation, targeted therapy and immunotherapy, lung cancer outcomes are transformed. We have to seek the appropriate medical attention at the earliest, be diagnosed promptly, understand the genomic subtype of the lung cancer case and embark of the most personalized.Myth: Lung cancer only affects older adults.Fact: Although age is a risk factor, lung cancer incidence is rising among younger adults, particularly women and especially amongst non-smokers. Driver mutation positive lung cancers are seen in younger adults and also has chances of metastasis to the brain. Extra attention should be paid in young patients who present with lung cancer, to search for driver mutations which should be treated with targeted therapy for transformed outcomes. The disease does not discriminate by age or gender, underscoring the need for enhanced awareness across all demographics.A Way ForwardEducating the public and dispelling myths surrounding lung cancer is essential in creating a culture of early detection and preventative health practices. Increasing awareness not only empowers individuals to take charge of their lung health but also reduces the stigma surrounding lung cancer—a crucial step in encouraging individuals to seek timely screenings.Advances in lung cancer treatment have revolutionized lung cancer outcomes. Prevention, early diagnosis and understanding which type of lung cancer the person has, are most critical in personalizing the therapeutic strategy to give the right treatment for improved outcomes and to prolong life. . By moving beyond misconceptions, we can foster a narrative that promotes early detection and early intervention, educates individuals on risk factors, and ultimately contributes to saving scores of lives.Dr Sewanti Limaye, Director, Medical & Precision Oncology, Sir HN Reliance Foundation Hospital, Mumbai, IndiaStay updated with the latest news on Times of India. Spread love this holiday season with these New Year wishes, messages, and quotes.

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Developing multiple EGFR-mutant lung cancers

The occurrence of multiple independent tumours in patients with EGFR-mutant lung cancer was unexplained. A recent study in Nature Cancer identified distinct genetic predisposition mechanisms, including developmental mosaicism and germline EGFR variants, that contribute to the formation of multiple primary tumours.

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