Although the majority of patients with metastatic non-small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS: Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS: Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P < .001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P < .001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders. CONCLUSION: Molecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies.
Although the majority of patients with metastatic non-small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS: Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS: Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P < .001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P < .001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders. CONCLUSION: Molecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies.
Authors: Sharyn I Katz; Mark Hammer; Stephen J Bagley; Charu Aggarwal; Joshua M Bauml; Jeffrey C Thompson; Arun C Nachiappan; Charles B Simone; Corey J Langer Journal: J Thorac Oncol Date: 2018-05-05 Impact factor: 15.609
Authors: M Tazdait; L Mezquita; J Lahmar; R Ferrara; F Bidault; S Ammari; C Balleyguier; D Planchard; A Gazzah; J C Soria; A Marabelle; B Besse; C Caramella Journal: Eur J Cancer Date: 2017-11-26 Impact factor: 9.162
Authors: Patrick A Ott; Yung-Jue Bang; Sarina A Piha-Paul; Albiruni R Abdul Razak; Jaafar Bennouna; Jean-Charles Soria; Hope S Rugo; Roger B Cohen; Bert H O'Neil; Janice M Mehnert; Juanita Lopez; Toshihiko Doi; Emilie M J van Brummelen; Razvan Cristescu; Ping Yang; Kenneth Emancipator; Karen Stein; Mark Ayers; Andrew K Joe; Jared K Lunceford Journal: J Clin Oncol Date: 2018-12-13 Impact factor: 44.544
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Melanie A Leiby; Gregory M Lubiniecki; Yue Shentu; Reshma Rangwala; Julie R Brahmer Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Luis Paz-Ares; Alexander Luft; David Vicente; Ali Tafreshi; Mahmut Gümüş; Julien Mazières; Barbara Hermes; Filiz Çay Şenler; Tibor Csőszi; Andrea Fülöp; Jerónimo Rodríguez-Cid; Jonathan Wilson; Shunichi Sugawara; Terufumi Kato; Ki Hyeong Lee; Ying Cheng; Silvia Novello; Balazs Halmos; Xiaodong Li; Gregory M Lubiniecki; Bilal Piperdi; Dariusz M Kowalski Journal: N Engl J Med Date: 2018-09-25 Impact factor: 91.245
Authors: Justin I Odegaard; John J Vincent; Stefanie Mortimer; James V Vowles; Bryan C Ulrich; Kimberly C Banks; Stephen R Fairclough; Oliver A Zill; Marcin Sikora; Reza Mokhtari; Diana Abdueva; Rebecca J Nagy; Christine E Lee; Lesli A Kiedrowski; Cloud P Paweletz; Helmy Eltoukhy; Richard B Lanman; Darya I Chudova; AmirAli Talasaz Journal: Clin Cancer Res Date: 2018-04-24 Impact factor: 12.531
Authors: Richard B Lanman; Stefanie A Mortimer; Oliver A Zill; Dragan Sebisanovic; Rene Lopez; Sibel Blau; Eric A Collisson; Stephen G Divers; Dave S B Hoon; E Scott Kopetz; Jeeyun Lee; Petros G Nikolinakos; Arthur M Baca; Bahram G Kermani; Helmy Eltoukhy; AmirAli Talasaz Journal: PLoS One Date: 2015-10-16 Impact factor: 3.240
Authors: Matthew D Hellmann; Tavi Nathanson; Hira Rizvi; Benjamin C Creelan; Francisco Sanchez-Vega; Arun Ahuja; Ai Ni; Jacki B Novik; Levi M B Mangarin; Mohsen Abu-Akeel; Cailian Liu; Jennifer L Sauter; Natasha Rekhtman; Eliza Chang; Margaret K Callahan; Jamie E Chaft; Martin H Voss; Megan Tenet; Xue-Mei Li; Kelly Covello; Andrea Renninger; Patrik Vitazka; William J Geese; Hossein Borghaei; Charles M Rudin; Scott J Antonia; Charles Swanton; Jeff Hammerbacher; Taha Merghoub; Nicholas McGranahan; Alexandra Snyder; Jedd D Wolchok Journal: Cancer Cell Date: 2018-04-12 Impact factor: 31.743
Authors: Mohamed A Gouda; Helen J Huang; Sarina A Piha-Paul; S Greg Call; Daniel D Karp; Siqing Fu; Aung Naing; Vivek Subbiah; Shubham Pant; Derek J Dustin; Apostolia M Tsimberidou; David S Hong; Jordi Rodon; Funda Meric-Bernstam; Filip Janku Journal: JCO Precis Oncol Date: 2022-07
Authors: Philip C Mack; Jieling Miao; Mary W Redman; James Moon; Sarah B Goldberg; Roy S Herbst; Mary Ann Melnick; Zenta Walther; Fred R Hirsch; Katerina Politi; Karen Kelly; David R Gandara Journal: Clin Cancer Res Date: 2022-09-01 Impact factor: 13.801
Authors: Jeffrey C Thompson; Charu Aggarwal; Janeline Wong; Vivek Nimgaonkar; Wei-Ting Hwang; Michelle Andronov; David M Dibardino; Christoph T Hutchinson; Kevin C Ma; Anthony Lanfranco; Edmund Moon; Andrew R Haas; Aditi P Singh; Christine A Ciunci; Melina Marmarelis; Christopher D'Avella; Justine V Cohen; Joshua M Bauml; Roger B Cohen; Corey J Langer; Anil Vachani; Erica L Carpenter Journal: JTO Clin Res Rep Date: 2022-03-08
Authors: Shadma Fatima; Yafeng Ma; Azadeh Safrachi; Sana Haider; Kevin J Spring; Fatemeh Vafaee; Kieran F Scott; Tara L Roberts; Therese M Becker; Paul de Souza Journal: Cancers (Basel) Date: 2022-03-25 Impact factor: 6.639
Authors: Diana Merino Vega; Katherine K Nishimura; Névine Zariffa; Jeffrey C Thompson; Antje Hoering; Vanessa Cilento; Adam Rosenthal; Valsamo Anagnostou; Jonathan Baden; Julia A Beaver; Aadel A Chaudhuri; Darya Chudova; Alexander D Fine; Joseph Fiore; Rachel Hodge; Darren Hodgson; Nathan Hunkapiller; Daniel M Klass; Julie Kobie; Carol Peña; Gene Pennello; Neil Peterman; Reena Philip; Katie J Quinn; David Raben; Gary L Rosner; Mark Sausen; Ayse Tezcan; Qi Xia; Jing Yi; Amanda G Young; Mark D Stewart; Erica L Carpenter; Charu Aggarwal; Jeff Allen Journal: JCO Precis Oncol Date: 2022-08