The PROSPECT-Lung trial has officially commenced, heralding a significant advance in the quest to enhance treatment strategies for patients with resectable non-small cell lung cancer (NSCLC). This trial marks the inaugural endeavor of the newly established National Cancer Institute (NCI) Clinical Trials Innovation Unit (CTIU). The primary objective of this large, multicenter trial, spearheaded by the Alliance for Clinical Trials in Oncology and the SWOG Cancer Research Network within the NIH-funded NCI National Clinical Trials Network (NCTN), aims to assess the role of immunotherapy when administered before and after surgery in patients with resectable NSCLC. By exploring the efficacy of immunotherapy in conjunction with surgery, the trial seeks to provide compelling evidence that could potentially redefine standard care protocols for early-stage lung cancer patients.
The Significance of the PROSPECT-Lung Trial
The PROSPECT-Lung trial is poised to determine whether incorporating immune checkpoint inhibitors into the standard chemotherapy regimen, either preoperatively or postoperatively, can prolong survival and prevent cancer recurrence in patients with early-stage, resectable NSCLC. Additionally, the trial aims to evaluate if perioperative immunotherapy, provided both before and after surgery, proves to be more effective compared to adjuvant therapy alone. Lung cancer remains the predominant cause of cancer-related deaths among both men and women, accounting for approximately 20% of all cancer fatalities. NSCLC represents 80-85% of lung cancer cases, with the remaining cases classified as small cell lung cancer. Early detection of lung cancer frequently occurs incidentally during imaging for unrelated health issues. Despite early diagnosis and intervention through surgery and chemotherapy, cancer recurrence is common. Thus, identifying ways to enhance treatment efficacy remains crucial.
Daniel Morgensztern, MD, Alliance Study Co-Chair and Professor in the Division of Medical Oncology at Washington University’s Siteman Cancer Center, stressed the trial’s significance. He stated that testing the optimal timing of immunotherapy pre- and post-surgery would potentially offer clear guidance on integrating these novel therapies into treatment protocols for resectable lung cancer, ultimately improving patient outcomes and survival rates. The trial’s rationale is built upon promising data from previous studies indicating that immune checkpoint inhibitors combined with chemotherapy may enhance survival rates in lung cancer patients. This hypothesis is believed to hold true when administered in neoadjuvant (before surgery), adjuvant (after surgery), or perioperative (both before and after surgery) settings. However, a pivotal question remains unanswered: Should immune checkpoint inhibitors be administered pre- or post-surgical resection? The trial is methodically designed to address and resolve this critical query.
Real-World Treatment Scenarios and Trial Design
Supporting the significance of the trial’s innovative design, Raid Aljumaily, MD, SWOG Study Co-Chair and Associate Professor in the Division of Hematology/Oncology at the University of Oklahoma’s OU Health Stephenson Cancer Center, highlighted that this trial mirrors real-world treatment scenarios. By implementing a pragmatic design, the trial seeks to generate scientifically rigorous evidence applicable to everyday clinical practice, thereby defining the optimal approach for integrating immunotherapy into standard care for resectable NSCLC. The PROSPECT-Lung trial aligns with the broader mission of the CTIU, which was launched in February 2023 with an aim to expedite the development of innovative cancer treatments through collaboration, efficiency, and cutting-edge science. The CTIU strives to address high-priority clinical research needs by designing trials that are simpler and more inclusive, thereby reducing the burden on patients and investigators. PROSPECT-Lung is among the first studies supported by the CTIU, benefiting from its commitment to enhancing the speed and efficacy of clinical trials.
Michael LeBlanc, PhD, SWOG Group Statistician, and Professor of Biostatistics at the Fred Hutchinson Cancer Center, expressed enthusiasm about the PROSPECT-Lung trial’s initiation. Sumithra Mandrekar, PhD, Alliance Group Statistician, and Professor of Biostatistics and Oncology at the Mayo Clinic, elaborated that the trial’s innovative design is intended to streamline both endpoints and data collection, aligning with the NCI-CTAC Streamlining Clinical Trials Working Group’s initiatives. By mirroring data collection processes in electronic medical records, the trial aims to produce highly relevant and applicable results. David Kozono, MD, PhD, Executive Officer of the Alliance Respiratory Committee and Associate Professor of Radiation Oncology at Dana-Farber/Harvard Cancer Center, underscored the trial’s objective of addressing the vital question regarding the timing of immunotherapy in conjunction with surgery for stage II-III NSCLC. He noted that this type of question is often overlooked by pharmaceutical-company-sponsored research but fits well within the scope of the NCI-sponsored National Clinical Trials Network.
Collaborative Efforts and Future Implications
Raid Aljumaily, MD, SWOG Study Co-Chair and Associate Professor at OU Health Stephenson Cancer Center, emphasized the PROSPECT-Lung trial’s real-world relevance due to its pragmatic design. This approach aims to produce scientifically robust evidence that can be directly applied in everyday clinical practice, optimizing immunotherapy integration for resectable NSCLC. The trial complements CTIU’s mission, initiated in February 2023, focused on accelerating innovative cancer treatments through collaborative, efficient, and advanced scientific methods. CTIU aims to address key clinical research needs by crafting more straightforward and inclusive trials, reducing burdens on patients and researchers. As one of the first studies supported by CTIU, PROSPECT-Lung benefits from a commitment to enhance clinical trial speed and effectiveness.
Michael LeBlanc, PhD, at Fred Hutchinson Cancer Center, expressed enthusiasm for the trial. Sumithra Mandrekar, PhD, of the Mayo Clinic, highlighted the trial’s streamlined design. David Kozono, MD, PhD, at Dana-Farber/Harvard, stressed its importance in studying immunotherapy timing with surgery for stage II-III NSCLC, a question often overlooked by pharmaceutical research but pertinent to NCI-sponsored trials.
