LBA 08 - Comprehensive Patient Reported Outcomes (PROs) from NRG LU005: A Randomized Trial Of Chemoradiation (CRT) +/- Atezolizumab In Limited-Stage Small Cell Lung Cancer (LS-SCLC)
Presenter(s)
B. Movsas1, C. Hu2,3, K. A. Higgins4, H. J. Ross5, S. K. Jabbour6, D. E. Kozono7, T. K. Owonikoko8, C. Xiao9, T. Shoji10, B. Faller11, P. Mohindra12, E. G. Dib13, J. M. Brownstein14, S. G. Chun15, C. Kuzma16, R. Kotecha17, A. A. Onitilo18, R. Paulus19, J. D. Bradley20, and D. W. Bruner9; 1Henry Ford Cancer Institute, Detroit, MI, 2NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 3Johns Hopkins University School of Medicine, Baltimore, MD, 4City of Hope, Atlanta, GA, 5Rush University Medical Center, Chicago, IL, 6Rutgers Cancer Institute, New Brunswick, NJ, 7Dana-Farber/Harvard Cancer Center, Boston, MA, 8University of Maryland/Greenebaum Cancer Center, Baltimore, MD, 9Emory University Hospital/Winship Cancer Institute, Atlanta, GA, 10Hokkaido University, Sapporo, Japan, 11Heartland NCORP - Missouri Baptist Medical Center, St. Louis, MO, 12University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, OH, 13Trinity Health Cancer Center, Ann Arbor, MI, 14Ohio State University Comprehensive Cancer Center, Columbus, OH, 15MD Anderson Cancer Center, Houston, TX, 16First Health of the Carolinas Cancer Center, Pinehurst, NC, 17Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 18Marshfield Medical Center - Weston, Weston, WI, 19The American College of Radiology, Philidelphia, PA, 20University of Pennsylvania/Abramson Cancer Center, Philadelphia, PA
Purpose/Objective(s): While NRG-LU005 showed no overall survival (OS) advantage with the addition of immunotherapy (IO) to CRT, it found a median OS improvement for BID vs qday RT (35.4 vs 28.3 months). This planned analysis assessed longitudinal PROs. The pre-specified hypothesis was that clinically meaningful decline (CMD) in long-term PROs (at 15+ months after CRT) would be lower with IO, as measured by the Functional Assessment of Cancer Therapy – Trial Outcome Index (FACT-TOI).
Materials/Methods: Patients (N=544) were randomized to standard CRT (platinum/etoposide q3 weeks x 4 cycles + thoracic RT [45 Gy BID or 66 Gy daily] starting @ cycle 2 of chemo) +/- atezolizumab q3 weeks x 1 year starting @ cycle 2 of chemo. Stratification factors (SFs) included RT schedule (BID vs daily), chemo type (cisplatin vs carboplatin), sex, and ECOG performance status (PS). PROs included validated instruments: FACT-TOI, EQ-5D-5L (for Quality Adjusted Survival [QAS]), and PROMIS-Fatigue, administered at baseline, end of CRT, and at 3, 6, 15, and 21 months post-CRT. CMD in FACT-TOI was defined as a =5 point decline from baseline. QAS was estimated using EQ-5D-5L index scores and restricted mean survival. CMD and longitudinal trends were evaluated; multivariable logistic regression analysis (MVA) adjusted for treatment arm, SFs, and baseline FACT-TOI.
Results: PRO compliance exceeded 85% at baseline and stabilized at 60-68% through 21 months. Higher completion correlated with better baseline PS and pulmonary function. FACT-TOI declined on both arms during CRT, but improved by 3 months and remained stable or exceeded baseline by 6-21 months. While FACT-TOI changes from baseline were similar at 15 months on both arms, fewer patients on the IO arm had CMD (25% vs. 38%) at 21 months. EQ-5D-5L showed similar QAS in both arms. PROMIS-fatigue showed no increased fatigue with IO. ~50% of all patients received BID RT, which was associated with better QOL than qday RT across all timepoints, including significantly lower CMD at end of CRT (36% vs 60%), 15 months (28% vs 41%) and 21 months (22% vs 39%). On MVA, significant predictors of lower CMD (in addition to baseline FACT-TOI) included BID RT (at end of CRT, 15, 21 months), cisplatin (at 15 months), and IO (at 21 months).
Conclusion: As hypothesized, the addition of atezolizumab to CRT was associated with clinically meaningful improvements in longer term QOL (FACT-TOI), as well similar QAS with no negative impact on fatigue. To our knowledge, this is the first large trial to show that BID (vs daily) RT was associated with not only improved median OS, but also consistently more favorable PRO trajectory with significantly lower CMD in FACT-TOI. Conducted in the context of modern RT (IMRT ~90%), this analysis helps to address lingering concerns about BID RT’s impact on QOL and provides further support for BID RT in LS-SCLC directly from the patient perspective.