TY - JOUR
T1 - Impact of FDG PET imaging for expanding patient eligibility and measuring treatment response in a genome-driven basket trial of the Pan-HER kinase inhibitor, neratinib
AU - Ulaner, Gary A.
AU - Saura, Cristina
AU - Piha-Paul, Sarina A.
AU - Mayer, Ingrid
AU - Quinn, David
AU - Jhaveri, Komal
AU - Stone, Ben
AU - Shahin, Seta
AU - Mann, Grace
AU - Dujka, Melanie
AU - Bryce, Richard
AU - Meric-Bernstam, Funda
AU - Solit, David B.
AU - Hyman, David M.
N1 - Funding Information:
This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and Cycle for Survival. This work was supported by Puma Biotechnology. The authors thank the patients and families for participating in this study. Editorial support was provided by Lee Miller.
Funding Information:
G.A. Ulaner is an employee/paid consultant for Sanofi, and reports receiving commercial research grants from Puma. C. Saura is an advisory board member/ unpaid consultant for Puma Biotechnology. S.A. Piha-Paul reports receiving other commercial research support from Abbvie, Aminex Therapeutics, Bio-Marin Pharmaceutical, Boehringer-Ingelheim, Cerulean Pharma, Chugai, Curis, Five Prime Therapeutics, Genmab A/S, GlaxoSmithKline, Helix BioPharma, Incyte, Jacobi Pharmaceuticals, Medimmune, Medication, Merck Sharp and Dohme, NewLink Genetics Corp/Blue Link Pharmaceuticals, NewLink Genetics/Blue Link, Novartis, Pieris, Pfizer, Principia, Puma, Rapt, Seattle Genetics, Taiho, Tesaro, TransThera Bio, and XuanZhu Biopharma, I. Mayer is an employee/paid consultant for Eli-Lilly, Novartis, GlaxoSmithKline, Immuno-medics, Macrogenics, Seattle Genetics, AstraZeneca, and reports receiving commercial research grants from Genentech, Pfizer, and Novartis. D. Quinn is an employee/paid consultant for AstraZeneca, Genentech/Roche, Pfizer, and Novartis. K. Jhaveri is an advisory board member/unpaid consultant for Novartis, Pfizer, AstraZeneca, Genentech, Taiho Oncology, Juno Therapeutics, SpecSpectrum Pharmaceuticals, ADC Therapeutics, and Synthon. M. Dujka and R. Bryce are employee/paid consultants for and hold ownership interest (including patents) in Puma Biotechnology. F. Meric-Bernstam is an employee/paid consultant for Genetech, Pieris Pharmaceuticals, Samsung Bioepis, Aduro, OrigMed, Debiopharm Group, Zencor, Jackson Laboratory, Zymeworks, Inflection Bioscience, Darwin Health, Spectrum, Mersana, and Seattle Genetics, reports receiving commercial research grants from Novartis; AstraZeneca; Taiho Pharmaceutical; Genentech; Calithera Biosciences; Debiopharm Group; Bayer; Aileron, reports receiving speakers bureau honoraria from Chugai, and is an advisory board member/unpaid consultant for Taiho, Genentech, Debiopharm Group, Pfizer. D. Solit is an employee/paid consultant for Pfizer, Loxo Oncology, Illumina, Vivideon Therapeutics, and Lilly Oncology. D.M. Hyman is an
Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2019/12/15
Y1 - 2019/12/15
N2 - Purpose: To determine whether FDG PET can expand eligibility in biomarker-selected clinical trials by providing a means to quantitate response in patients with non-assessable disease by RECIST. Experimental Design: SUMMIT (NCT01953926) is a multicenter phase II "basket" trial of the Pan-HER kinase inhibitor, neratinib. Patients had advanced ERBB2 (HER2)-mutant solid tumors, ≥1 measurable lesion, preferably defined unidimensionally by RECIST v1.1, or alternatively metabolically by PET Response Criteria (PRC). The primary aim was to determine the proportion of additional breast cancer patients accrued using PRC who would have otherwise been ineligible based on RECIST criteria alone. The secondary aim was to determine the concordance of response versus non-response between RECIST and PRC. Results: Eighty-one patients with HER2-mutant metastatic breast cancer were accrued; 77 were evaluable for response by RECIST and/or PRC. 63 (82%) were RECIST-evaluable and 14 (18%) were accrued using PRC alone. Bone-only disease (n = 11; 79%) was the most common reason for classification as non-measurable by RECIST. Twenty-nine patients were accrued and followed using both criteria, of which 25 (86%; 95% confidence interval, 68%–96%) were concordant for response versus non-response as defined by RECIST and PRC. Conclusions: PRC allowed patients with non-RECIST measurable disease access to therapy and facilitated more rapid accrual of patients to this trial of a rare biomarker. PRC and RECIST both provided methods of response assessment and were generally concordant. Thus, PRC was useful as a supplement to RECIST criteria. This provides a rationale for including FDG PET measurements in future clinical trials involving rare tumors or rare genomically defined subpopulations of more common cancers.
AB - Purpose: To determine whether FDG PET can expand eligibility in biomarker-selected clinical trials by providing a means to quantitate response in patients with non-assessable disease by RECIST. Experimental Design: SUMMIT (NCT01953926) is a multicenter phase II "basket" trial of the Pan-HER kinase inhibitor, neratinib. Patients had advanced ERBB2 (HER2)-mutant solid tumors, ≥1 measurable lesion, preferably defined unidimensionally by RECIST v1.1, or alternatively metabolically by PET Response Criteria (PRC). The primary aim was to determine the proportion of additional breast cancer patients accrued using PRC who would have otherwise been ineligible based on RECIST criteria alone. The secondary aim was to determine the concordance of response versus non-response between RECIST and PRC. Results: Eighty-one patients with HER2-mutant metastatic breast cancer were accrued; 77 were evaluable for response by RECIST and/or PRC. 63 (82%) were RECIST-evaluable and 14 (18%) were accrued using PRC alone. Bone-only disease (n = 11; 79%) was the most common reason for classification as non-measurable by RECIST. Twenty-nine patients were accrued and followed using both criteria, of which 25 (86%; 95% confidence interval, 68%–96%) were concordant for response versus non-response as defined by RECIST and PRC. Conclusions: PRC allowed patients with non-RECIST measurable disease access to therapy and facilitated more rapid accrual of patients to this trial of a rare biomarker. PRC and RECIST both provided methods of response assessment and were generally concordant. Thus, PRC was useful as a supplement to RECIST criteria. This provides a rationale for including FDG PET measurements in future clinical trials involving rare tumors or rare genomically defined subpopulations of more common cancers.
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U2 - 10.1158/1078-0432.CCR-19-1658
DO - 10.1158/1078-0432.CCR-19-1658
M3 - Article
C2 - 31548342
AN - SCOPUS:85076503735
SN - 1078-0432
VL - 25
SP - 7381
EP - 7387
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -