Part I

Each June, the American Society of Clinical Oncology holds its annual meeting in Chicago, one of only two or three cities in the U.S. that has sufficient convention and hotel facilities to accommodate the over 40,000 attendees. The most important advances of the year, which will impact how cancer is treated going forward, are presented here. I did not attend in person, but will highlight in two articles this week and next some of the key studies (in my view). Over 5,000 studies are submitted to the meeting and 2,500 presented either orally or as poster presentations:

• This was a banner year for lung cancer studies. Suresh Ramalingam of the Winship Cancer Institute at Emory University in Atlanta presented a lung cancer study in the plenary session (of the 2500 studies presented, the six considered the most significant are selected for the plenary session). Advanced lung cancer has a poor prognosis with conventional chemotherapy (up to one year survival on average). However, about 10-15% of adenocarcinomas of the lung have a tumor marker on their pathology known as a mutation of the epidermal growth factor receptor (EGFR). The presence of this marker on the tumor makes it sensitive to certain drugs, notably osimertinib (Tagrisso)—with this treatment, they can have survivals of years in the metastatic setting. The current study further expanded our understanding of the use of osimertinib as adjuvant therapy in patients with EGFR-mutated lung cancer. The LAURA study randomized patients with unresectable stage III non small cell lung cancer (NSCLC) with EGFR mutations who had been treated with definitive platinum-based chemoradiotherapy and had not progressed to receive either osimertinib (n=143) or placebo (n=73) until progression. The median progression-free survival (PFS) was 39.1 months for osimertinib versus 5.6 months for placebo, and there was a trend towards an improvement in overall survival. The authors concluded that this established a new standard of care for the use of osimertinib for patients in this setting.
• Benjamin Solomon from the Peter McCallum Cancer Centre in Melbourne, Australia, reported on the 5-year results of the CROWN trial. Similar to EGFR, approximately 5% of NSCLC have a mutation in the ALK gene. Those who have this marker have been shown to be responsive to the immunotherapy drug crizotinib (Xalkori). This study randomized 296 patients with ALK-positive untreated advanced NSCLC to lorlatinib (Lorbrena) versus crizotinib—the progression-free survival (PFS) was 60% and 8%, respectively after 60 months of follow-up; the hazard ratio for progression was 0.19 (95% confidence interval (CI) 0.13-0.27). Equally remarkable, lorlatinib was associated with a 92% reduction in intracranial progression also. These studies illustrate the incredible power that molecular testing is conferring on the treatment of these tumors.
• Yet a third lung cancer study investigated the role of durvalumab for small cell lung cancer (SCLC), a subtype of lung cancer that comprises about 15% of lung cancer. This was another study presented at the plenary session by David Spigel of the Sarah Cannon Research Institute in Nashville, Tennessee. The ADRIATIC study enrolled patients with limited stage SCLC who received conventional platinum-based chemoradiotherapy with or without prophylactic cranial irradiation. Those who had not progressed were then randomized to one of three arms—durvalumab + tremelimumab; durvalumab + placebo; or placebo + placebo until progression or up to 24 months. The current study assessed durvalumab (Imfinzi) (n=264) versus placebo (n=266) at the pre-planned interim analysis, with a median follow-up of 37 months. The median PFS was 16.6 months for durvalumab vs 9.2 months for placebo (HR 0.76, 95%CI 0.61-0.95); the median overall survival was 55.9 months for durvalumab versus 33.4 months for placebo (HR 0.73, 95%CI 0.57-0.93). The rate of severe adverse effects was similar in both groups. The investigators concluded that durvalumab should now be a standard of care for patients with limited stage SCLC after chemoradiation.
• A groundbreaking study published by Jennifer Temel and colleagues in 2010 demonstrated that the provision of early palliative consultations to patients with stage IV lung cancer led to significant improvements in quality of life, and this recommendation has been incorporated into national guidelines. Nonetheless, this intervention has not been widely adopted. Temel and colleagues at the Massachusetts General Hospital in Boston presented two studies to increase implementation. Joseph Greer presented at the plenary session a randomized trial in which 1250 patients at 22 cancer centers with advanced NSCLC within 12 weeks of diagnosis were recruited over five years. They were randomized to meet with a palliative care clinician every four weeks either by telephone or in person. At 24 weeks, the quality of life scores were equivalent in the two groups, suggesting that telephone consultations could be effectively utilized. In a second randomized trial, Temel enrolled 507 patients with advanced NSCLC between February 2018 and December 2022 at three cancer centers. In this trial, patients were randomized to a simplified, stepped palliative care (SPC) or to the usual palliative care visit every 4 weeks. Patients in the SPC arm, after the initial visit, met with the palliative care physician only at the time of a change in cancer treatment or after a hospitalization. At 24 weeks, the mean number of physician visits was lower for the SPC arm than the usual care arm (2.44 vs 4.70, p>0.0001). In addition, the quality of life scores were non-inferior for the intervention arm. These two studies—one employing telehealth, and the other a stepped approach—demonstrated that palliative care could be effectively delivered with less resource intensity.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.