National Fellows Forum Showcases Next Generation of Lung Cancer Clinicians

Amanda Herrmann, MD

For oncology and hematology fellows looking to showcase their work and stay abreast of research conducted by other fellows from across the country, the OncLive National Fellows Forum series represents an opportunity to travel, make connections, and listen to intriguing presentations across clinical specialties.

During a recent OncLive National Fellows Forum on Lung Cancer, Amanda Herrmann, MD; Chinmay Jani, MD; and Cameron Oswalt, MD, conducted presentations tackling a variety of issues in the lung cancer space, including the time cost patients face during clinical trial participation, the evolving effect of air quality on lung cancer mortality rates, and the importance of palliative care in the modern treatment landscape. Herrmann is an oncology fellow at UC San Diego School of Medicine in California, Jani is a hematology/oncology fellow at Sylvester Comprehensive Cancer Center in Miami, Florida, and Oswalt is a hematology/oncology fellow at Duke University School of Medicine in Durham, North Carolina.

“I was honored to have the opportunity to attend, and having it be set in the days leading into [the 2024] ASCO [American Society of Clinical Oncology Annual Meeting] was a great warm-up for the large conference that came the following weekend,” Herrmann said in an interview with Oncology Fellows. “I had a great experience. It was a good opportunity to learn from an esteemed panel of faculty leaders in the field of thoracic oncology, as well as a group of about 20 fellows with similar interests and ambitions to my own. The opportunity to meet and to be among the people [and] to share my research with those individuals was invaluable.”

Combating Time Toxicity in Lung Cancer Clinical Trials

Herrmann’s presentation, which was the top-scoring presentation of the event, was concerned with quantifying \ patient-level time costs during clinical trials in lung cancer. TIME TOX Lung was a retrospective, proof-of-concept study that aimed to develop a standardized time-toxicity metric and evaluate the feasibility of applying it to clinical trial protocols.¹

To conduct her study, Hermann and her coauthors obtained study protocols from 32 clinical trials that supported the FDA approvals of 18 oral targeted lung cancer agents. Study-mandated procedures were assigned the standardized metric, time toxicity units (TTUs), based on the standard times dedicated to those procedures at UC San Diego or in published guidelines; 1 TTU was equivalent to 30 minutes. Investigators then multiplied the TTUs for each procedure according to their frequency; these then were totaled through 5 cycles to determine the total time toxicity score of a given trial. TIME TOX examined phase 1 (n = 8), phase 2 (n = 12), and phase 3 (n = 12) studies spanning 2005 to 2024.

Findings from the study demonstrated that the median total time toxicity score for all trials over the study period was 77.4 (range, 34.0-141.5). Notably, trials conducted from 2005 to 2014 (n = 7) had a median total time toxicity score of 40.3 (range, 34.0-109.3) compared with 80.0 (range, 40.7-141.5) for studies conducted from 2015 to 2024 (P = .045).

Overall, phase 1, 2, and 3 studies had median total time toxicity scores of 85.5 (range, 60.0-130.2), 73.4 (range, 51.7-141.5), and 73.3 (range, 34.0-109.3), respectively. These figures were 91.0 (range, 66.2-130.2), 73.4 (range, 51.7-141.5), and 84.4 (range, 40.7-98.7), respectively, in studies that occurred from 2015 to 2024. From 2005 to 2014, the median total time toxicity score was 60.0 (range, 60.0-60.0) in phase 1 trials and 40.3 (range, 34.0-109.3) in phase 3 trials; no phase 2 data were available.

Hermann plans to expand her current data set to encompass all FDA-approved therapies for advanced or metastatic non–small cell lung cancer (NSCLC). She also wants to validate the metric by applying it prospectively to studies conducted at Moores Cancer Center at UC San Diego Health in California. In the future, she hopes that TTUs can be used as a standardized mechanism to streamline clinical trial protocol development and inform patients of the potential time toxicity of studies before enrollment.

Better Defining the Effect of Air Quality on Lung Cancer Incidence

Due in part to modernized attitudes and policies toward tobacco smoking, other lung cancer risk factors, such as air pollution, have come to the forefront of discussion, with instances of non–tobacco-related lung cancer increasing. To better characterize the effect of air pollution– and asbestos-associated lung cancer on disease mortality rates, Jani performed an observational study that gathered data from patients with tracheal, bronchial, and lung cancer from the 10 most populous countries in the world per the 2023 census spanning 1990 to 2019.²

Jani used a joinpoint regression analysis to determine the estimated annual percentage change in asbestos and particulate matter air pollution. Asbestos and particulate matter air pollution, including ambient air matter pollution and household air pollution from solid fuels, were examined as risk factors. Data were gathered from the Global Burden of Disease database; Jani calculated overall and risk factor–associated age-standardized mortality rates (ASMRs) by gender per 100,000 individuals.

“A major [development] of the past 2 to 3 decades in lung cancer mortality is that the risk factors leading to lung cancer have evolved,” Jani explained in an interview with Oncology Fellows. “There have been a lot of stricter tobacco-related policies reducing lung cancer because of tobacco [use]. [However,] other risk factors [such as] air pollution and occupational hazards are increasing in multiple countries. The main objective of our study was to analyze the trends of lung cancer mortality, particularly associated with risk factors such as tobacco and air pollution, and then stratify them even further.”

Data from the study showed that the overall ASMR globally decreased from 27.3 to 25.2 per 100,000 individuals from 1990 to 2019; however, the figure increased from 7.0 to 8.1 per 100,000 individuals, 31.2 to 38.7 per 100,000 individuals, 18.0 to 24.4 per 100,000 individuals, 14.7 to 17.2 per 100,000 individuals, and 6.8 to 8.3 per 100,000 individuals, in India, China, Indonesia, Pakistan, and Nigeria, respectively. During this time, asbestos-associated ASMR rose in India, from 0.3 to 0.5 per 100,000 individuals, China, from 0.8 to 1.3 per 100,000 individuals, Indonesia, from 0.2 to 0.9 per 100,000 individuals, and Pakistan, 0.3 to 0.6 per 100,000 individuals; air pollution–associated ASMR also rose in these nations from 2.5 to 2.6 per 100,000 individuals, 5.4 to 5.5 per 100,000 individuals, and 2.6 to 2.7 per 100,000 individuals, respectively. Asbestos- and air pollution– associated ASMR decreased or remained static in every other country that was evaluated.

However, ambient particulate matter–associated ASMR increased from 1990 to 2019 in most of the countries that were examined (n = 6). China, from 3.4 to 8.8 per 100,000 individuals, India, from 0.7 to 1.7 per 100,000 individuals, Indonesia, from 1.3 to 2.8 per 100,000 individuals, Pakistan, from 0.9 to 3.0 per 100,000 individuals, Nigeria, from 0.4 to 1.3 per 100,000 individuals, and Bangladesh, from 0.5 to 1.2 per 100,000 individuals, all saw significant increases in ambient particulate matter–associated ASMR during this period. Household air pollution– associated ASMR decreased in every nation over the study period except in the US where it remained at 0.0 per 100,000 individuals.

“Tobacco-associated lung cancer mortality has been proportionately reduced, but it’s still the most common lung cancer risk factor leading to mortality,” Jani said. “The evolving trend we are seeing in these recent years and decades is that air pollution–associated lung cancer mortality is significantly going up, and that’s concerning. We also [examined] household pollution and particulate matter pollution. It seems that the air pollution is becoming a major [factor] in lung cancer mortality.”

In the conclusion of his presentation, Jani noted that air pollution now represents the second-most common risk factor for tracheal, bronchial, and lung cancer, totaling nearly 20% of the proportional ASMR of these cancers globally. “There has been a huge drive for tobacco consumption reduction, but there isn’t much awareness for air pollution [as a lung cancer risk factor],” Jani added. “It’s a big factor for lung cancer mortality, not only in the urban population but also in the suburban and rural populations in different parts of the world. Different kinds of air pollution can be associated with lung cancer mortality; higher awareness and stricter policies are needed for air pollution.”

Working to Improve Palliative Care in NSCLC

The role of palliative care must continue to evolve and be personalized according to treatment selection in order to provide patients with NSCLC the best possible care, according to Oswalt. “Immunotherapy has permeated the treatment landscape. We’re continuing to advance care for patients with targeted therapies and other advancements. [Thus,] the role that palliative care has [in] patient management and care is shifting to where it’s not a straight or diagonal line. Now, you have blips, and as the patient’s care progresses, the role of palliative care ebbs and flows; if there’s a particular symptom that’s getting worse, palliative care may become more involved,” Oswalt explained in an interview with Oncology Fellows.

During the Fellows Forum event, Oswalt presented an analysis that examined the effects of the timing of palliative care involvement on patient experience and end-of-life outcomes. He gathered data from 152 patients diagnosed with metastatic NSCLC from the Duke Molecular Tumor Registry from March 2015 to June 2019; the study population consisted of 80 patients with no palliative care contact and 72 who saw a palliative care specialist. Within the palliative care group, patients were further divided by timing of palliative care consult (early [0-2 months] vs intermediate [2-6 months] vs late [6+ months]) and the number of palliative care visits (inpatient only vs 1-2 visits vs 3+ visits).

The overall population included patients treated with frontline chemotherapy (n = 39), chemotherapy plus immunotherapy (n = 46), a single immunotherapy agent (n = 27), or an immunotherapy doublet (n = 40). Within the palliative care arm, 22 patients were referred to palliative care early, 24 during the intermediate time frame, and 26 were referred late. Most patients in each subgroup had at least 3 palliative care visits (early, n = 14; intermediate, n = 13; late, n = 7), with 4 vs 4 vs 10 patients in each respective subgroup undergoing inpatient palliative care only and 4 vs 7 vs 9 patients in each respective subgroup having had 1 to 2 palliative care visits.³

“Even though previous data [showed] that early palliative care referrals led to improved quality of life and outcomes, we didn’t necessarily see that same trend [toward more] palliative care referral in our patient cohort, [possibly] due to patient preferences, preconceived notions, barriers to palliative care, and referrals,” Oswalt noted.

Overall, 72.4% of patients died during the study period, and 59.1% were enrolled in hospice care. Hospice enrollment rates were comparable among patients who did not receive palliative care (58.0%) vs those who received early (57.1%), intermediate (55.0%), and late (65.4%) palliative care. The death rates in these groups were 62.5%, 63.6%, 83.3%, and 100%, respectively.

Additionally, patients who received no palliative care experienced a median of 38.8 days on hospice care, received aggressive end-of-life care at a rate of 64%, and had an in-hospital death rate of 22%. In the palliative care group, patients who received inpatient, late, intermediate, and early care experienced median times on hospice of 24.9, 27.8, 27.9, and 53.6 days, respectively. The respective rates of aggressive end-of-life care were 73%, 62%, 65%, and 43%, and the respective rates of in-hospital death were 27%, 23%, 20%, and 14%.

“We ultimately found that patients who saw palliative care early had longer time on hospice, lower rates of aggressive end-of-life care, and they had lower rates of in-hospital deaths compared with the other groups of patients,” Oswalt said. “As we continue to improve our oncologic care, it’s always important to look at other ways that we can improve care [in terms of] the patient experience and the health system setting. What are the barriers to referrals to palliative care, both on the patient and the provider level? How can we work as a health system and as a multidisciplinary team to best identify the patients who are maybe not seeing palliative care and would benefit from that? Is the barrier at the patient, provider, or systems level, and what interventions can we employ to overcome some of those barriers and to identify them?”

References

1. Herrmann A, Bazhenova L. TIME TOX lung: retrospectively quantifying the timetoxicity of lung cancer clinical trials. Presented at: OncLive National Fellows Forum on Lung Cancer; May 30, 2024; Chicago, IL. Accessed August 9, 2024.
2. Jani C. Unraveling particulate matter and asbestos-associated lung cancer trends in the top ten most populous countries. Presented at: OncLive National Fellows Forum on Lung Cancer; May 30, 2024; Chicago, IL. Accessed August 9, 2024.
3. Oswalt C. Effects of timing of palliative care consultation on end of life care outcomes in mNSCLC. Presented at: OncLive National Fellows Forum on Lung Cancer; May 30, 2024; Chicago, IL. Accessed August 9, 2024.