Local Consolidative Therapy in Oligometastatic NSCLC With No Progression on First-line Systemic Treatment CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

Local Consolidative Therapy in Oligometastatic NSCLC: Background Evidence from preclinical and retrospective studies suggest that some pts with metastatic NSCLC may have a less aggressive or “limited metastatic” phenotype and may benefit from more aggressive therapy; this is known as “oligometastatic disease” The role of aggressive local therapy in this context remains controversial Not yet addressed in randomized trials Current multi-institutional phase II randomized trial evaluated efficacy of LCT for patients with oligometastatic NSCLC not progressing after first-line systemic therapy LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer. Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: Randomized Phase II Study Design Stratified by nodal status (NO/N1 vs N2/N3), EGFR/EML4-ALK status (yes/no), CNS metastases (yes/no), number of metastases (1 vs 2/3), and response to FLST (SD vs PR/CR) No Local Consolidative Therapy (n = 24) Histologically confirmed stage IV NSCLC, no RECIST progression after FLST, ≤ 3 metastases after FLST (n = 49) Standard maintenance or observation† Crossover allowed at PD Consider LCT (surgery ± radiation) FLST* (N = 74) PD/Toxicity Local Consolidative Therapy (n = 25) LCT (surgery ± radiation) Standard maintenance or observation† PD *≥ 4 cycles of platinum-doublet chemotherapy, or ≥ 3 mos of afatinib, erlotinib, or gefitinib in setting of EGFR mutation, or ≥ 3 mos of crizotinib if EML4-ALK fusion; pts could enroll before or during FLST, but randomization occurred after completion of FLST without progression. †Physician choice. CNS, central nervous system; FLST, first-line systemic therapy; LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors. Primary outcome: PFS Time from randomization to PD or death if endpoint met, time from randomization to last imaging if no progression, and censored at time of crossover due to toxicity Follow-up every 6-10 wks in Yr 1, then at physician’s discretion Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: Pt Characteristics Treatment arms well balanced with respect to age, race, sex, histology, and balanced prognostic factors Treatment Regimens in LCT Arm, n (%) Pts (N = 25) Hypofractionated RT/SBRT 13 (52) Combination CRT and hypofractionated RT 4 (16) Combination surgery and RT 3 (12) CRT alone Surgery alone 1 (4) Progressed prior to local treatment CRT, chemoradiotherapy; LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer; RT, radiotherapy; SBRT, stereotactic body radiation therapy. Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: PFS and OS Study closed by DSMC due to observed efficacy in the LCT arm after 49 patients randomized, at median follow-up of 18.7 months Median PFS No LCT : 3.9 mos (95% CI: 2.2-6.6) LCT: 11.9 mos (95% CI: 5.4-NA; P = .005) Other factors associated with improved PFS included number of metastases after FLST (1 vs 2 or 3; P = .043) and EGFR/ALK status (positive vs negative; P = .035) PFS benefit remained after censoring pts with EGFR/ALK alterations (HR: 0.41; 95% CI: 0.19-0.90; P = .022) Median OS not reached in either arm, and data not mature Deaths: 14 (6 in LCT arm; 8 in no-LCT arm) DSMC, data and safety monitoring committee; FLST, first-line systemic therapy; LCT, local consolidative therapy; NA, not available; NSCLC, non-small-cell lung cancer Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: Patterns of Failure Progression in 30 pts (61%), most often in new lesions (n = 14) or distant metastases (n = 16); progression at combination of new and known sites also common (n = 9) LCT arm had primarily distant and new lesion failures; no-LCT arm had more locoregional failures and combined new and known site failures Trend toward significance in patterns of failure (P = .09) Locoregional-only failures higher in no-LCT arm vs LCT arm (17% vs 4%) Metastatic-only failures higher in LCT arm vs no-LCT arm (40% vs 25%) Both locoregional/metastatic failures higher in no-LCT vs LCT arm (29% vs 8%) Median TNSF: 11.9 mos in LCT arm vs 5.7 mos in no-LCT arm (P = .0497) LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer; TNSF, time to new site failure. Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: Crossovers 3 crossovers prior to PD: fatigue, chemotherapy- related anemia, renal failure 17 pts had PD in no-LCT arm 11 crossed over and had LCT (6 hypofractionated RT/SBRT, 3 surgery only, 1 surgery/RT, 1 SBRT/chemoRT) LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer; PD, progressive disease; RT, radiotherapy; SBRT, stereotactic body radiotherapy. Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: Toxicity No substantial toxicity differences observed between arms No-LCT arm: 3 pts crossed over due to toxicity 1 anemia, 1 fatigue, 1 renal insufficiency 1 discontinuation due to bilateral edema of the lower extremities LCT arm Grade 3 esophagitis: 2 1 anemia, 1 pneumothorax, 1 pain LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer. Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

LCT in Oligometastatic NSCLC: Conclusions LCT associated with improved PFS in pts with oligometastatic NSCLC and no progression after FLST Limitations include small pt number, pt/treatment heterogeneity, and select group of pts represented In exploratory analyses, LCT increased time to development of new lesions, suggesting that this strategy reduces metastatic spread LCT toxicity profile acceptable and not substantially different from that of no-LCT arm FLST, first-line systemic therapy; LCT, local consolidative therapy; NSCLC, non-small-cell lung cancer. Slide credit: clinicaloptions.com Gomez DR, et al. ASCO 2016. Abstract 9004.

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