- Email: [email protected]
Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK+ NSCLC from ALTA-1L
abstracts
Annals of Oncology
O1 2 4
Efficacy of nivolumab for head and neck cancer arising from subsites which were not included in CheckMate 141
Yuri Ueda, Takao Fujisawa, Kazue Ito, Tomohiro Enokida, Susumu Okano, Makoto Tahara Department of Head and Neck Medical Oncology, National Cancer Center East, Japan Background: In the CheckMate 141 trial, nivolumab, a human IgG4 anti-PD-1 monoclonal antibody, provided a significant improvement in overall survival (OS) of patients with recurrent or metastatic squamous cell carcinoma (SCC) of the oral cavity, pharynx, or larynx. In Japan, nivolumab has been approved for platinum pretreated head and neck cancers regardless of histologic type and subsite. In other words, nivolumab is also available for non-SCC and subsites of head and neck cancer which were not included in the CheckMate 141 trial. However, the efficacy of nivolumab for cancers arising from these other subsites has not been clarified. Methods: We retrospectively reviewed data for 122 consecutive patients with head and neck cancers treated with nivolumab in our institution between March 2017 and December 2018. Patients with head and neck SCC of oral, oropharyngeal, hypopharyngeal, and laryngeal cancer were excluded. Final analysis of the study population was restricted to those 37 patients with non-SCC histological type or SCC arising from other subsites of the head and neck. Results: Median age was 57 years (range 30 to 77). Primary sites were nasopharynx/ sinonasal/salivary/other regions of the head and neck (n ¼ 8/10/8/11). Nineteen patients had SCC and 18 had non-SCC. In patients who could be evaluated by RECIST (n ¼ 32), objective response rate was 18.8% in the total study population, 37.5% in NPC, 10.0% in sinonasal cancer and 25.0% in salivary cancer. Median OS and time to treatment failure (TTF) in the total study population was 12.1 months and 2.3 months, respectively. Median TTF in NPC patients was better than that in patients with other primary sites (7.6 vs. 2.5 months, p ¼ 0.016). There was a trend toward improved TTF in SCC group compared to non-SCC group (4.2 vs. 2.4 months, p ¼ 0.31). Conclusion: Nivolumab showed favorable efficacy in head and neck cancers arising from subsites which were not included in the CheckMate141 trial, especially NPC patients.
O1 4 1
Effects of Dose Modifications on Safety and Efficacy of Dacomitinib for EGFR1 NSCLC in ARCHER 1050 Japanese Subset
Terufumi Kato1, Makoto Nishio2, Seiji Niho3, Noboru Yamamoto4, Toshiaki Takahashi5, Naoyuki Nogami6, Hiroyasu Kaneda7, Yuka Fujita8, Keith Wilner9, Mizuki Yoshida10, Mitsuhiro Isozaki10, Shinsuke Wada11, Fumito Tsuji12, Kazuhiko Nakagawa13 1 Kanagawa Cancer Center, Japan, 2The Cancer Institute Hospital of JFCR, 3National Cancer Center Hospital East, 4National Cancer Center Hospital, 5Shizuoka Cancer Center, 6Shikoku Cancer Center, 7Osaka City University, 8Asahikawa Medical Center, 9 Pfizer Oncology, 10Pfizer Research and Development Japan Biometrics and Data Management, 11Pfizer Research and Development Japan Clinical Research, 12SFJ Pharma Japan K.K, 13Kindai University Hospital Background: Dacomitinib (d) is effective first-line (1L) therapy in patients (pts) with EGFR-mutation-positive (EGFRþ) advanced NSCLC. In the ARCHER 1050 study (NCT01774721), 1L treatment with d was manageable and resulted in clinically meaningful, statistically significant improvement in PFS vs gefitinib (g). Here we present results for Japanese pts from ARCHER 1050. Methods: Pts with newly diagnosed stage IIIB/IV or recurrent EGFRþ advanced NSCLC were randomized to once-daily (qd) oral d 45 mg or g 250 mg. Randomization was stratified by race and EGFR mutation subtype. The primary endpoint was PFS. All pts enrolled were part of the efficacy analysis. Pts who received 1 dose of study drug were part of the safety analysis. Results: Of 452 total pts, 81 were Japanese; d (n ¼ 40), g (n ¼ 41). Median PFS was 18.2 mo for d (95% confidence interval [CI], 11.0-31.3) vs 9.3 mo for g (95% CI, 7.414.7). All 81 pts received study treatment. No grade (G) 4 or 5 adverse events (AEs) occurred in d-treated pts. Three G4 AEs (hepatic enzyme increases [n ¼ 2], suicide attempt) and a G5 AE (disease progression) occurred in g-treated pts. The most common G3 AEs were dermatitis acneiform (27.5%) and paronychia (22.5%) with d and ALT increased (12.2%) and abnormal hepatic function (7.3%) with g. Dose reduction occurred in 85% of d-treated pts; 24.4% of g-treated pts changed from qd to every other day dosing. Frequency and severity of special interest AEs (diarrhea, stomatitis, dermatitis and paronychia) were generally decreased after d dose reduction. Although the frequency of d dose modifications in Japanese pts was higher than in the ARCHER 1050 overall population, median treatment duration for pts who had d dose reductions was longer vs those who did not.
Volume 30 | Supplement 6 | October 2019
Conclusion: D significantly improved PFS over g in 1L treatment of Japanese pts with EGFRþ advanced NSCLC and had a manageable safety profile. Tolerability was improved and treatment duration was prolonged in pts who had their d dose reduced.
O1 4 2½Encore
Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK1 NSCLC from ALTA-1L
James CH Yang1, Hye R Kim2, Myung-Ju Ahn3, Ji-Youn Han4, Maximilian J Hochmair5, Ki H Lee6, Angelo Delmonte7, Maria R Garcia Campelo8, Dong-Wan Kim9, Enriqueta Felip10, Raffaele Califano11, Alexander Spira12, Scott Gettinger13, Marcello Tiseo14, Jeff Haney15, David Kerstein15, Sanjay Popat16, D R Camidge17 1 National Taiwan University Hospital, Taiwan, 2Yonsei University Severance Hospital, Seoul, South Korea, 3Samsung Medical Center, Seoul, South Korea, 4National Cancer Center, Goyang, South Korea, 5Department of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna, Austria, 6Chungbuk National University Hospital, Cheongju, South Korea, 7Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola, Italy, 8Complejo Hospitalario Universitario A Coruna Hospital Teresa Herrera-Materno Infantil, Coruna, Spain, 9Seoul National University Hospital, Seoul, South Korea, 10Vall d’Hebron University Hospital, Barcelona, Spain, 11The Christie NHS Foundation Trust, Manchester, England, United Kingdom, 12Virginia Cancer Specialists, Fairfax, VA, USA, 13Yale Cancer Center, New Haven, CT, USA, 14University Hospital of Parma, Parma, Italy, 15Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA, 16Royal Marsden Hospital, London, England, United Kingdom, 17University of Colorado Cancer Center, Aurora, CO, USA Background: We report results of the first interim analysis (IA) of BRG vs CRZ in ALK TKI-naive, ALKþ NSCLC from ALTA-1L (NCT02737501). Methods: This open-label, multicenter study enrolled pts with advanced ALKþ NSCLC who had 1 prior systemic therapy; asymptomatic CNS metastases were allowed. Pts were randomized 1:1 to BRG 180 mg QD with 7-day lead-in at 90 mg or CRZ 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed ORR, intracranial (i) ORR (iORR), and PFS (iPFS). IAs were planned at 50% and 75% of 198 expected PFS events. Results: 275 pts were randomized (BRG/CRZ, n ¼ 137/138); median age: 58/60 y. 26%/27% received prior chemotherapy for advanced disease; 29%/30% had baseline brain metastases. At data cutoff (19Feb2018), median follow-up of BRG/CRZ was 11.0/ 9.25 mo. With 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33-0.74, log-rank P¼0.0007); BRG median PFS (95% CI) was not reached (NR; NR) vs CRZ 9.8 months (9.0-12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30-0.68), log-rank P¼0.0001. Confirmed ORR for BRG was 71% (62-78) vs CRZ 60% (51-68). In pts with any iCNS disease (BRG/CRZ, n ¼ 43/47), confirmed iORR was 67% (51-81) vs 17% (831), P<0.0001. BRG median iPFS was NR (11 mo-NR) vs CRZ 6 mo (4-9); HR 0.27 (95% CI 0.13-0.54); log-rank P<0.0001. In pts with measurable iCNS disease (BRG/ CRZ, n ¼ 18/21), confirmed iORR was BRG 78% (52-94) vs CRZ 29% (11-52); P¼0.0028. Most common grade 3 TEAEs for BRG were increased CPK (16.2%) and lipase (13.2%), hypertension (9.6%), and for CRZ were increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis (BRG/CRZ): 3.7%/2.2%; discontinuations due to AE: 11.8%/8.8%. Conclusions: BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor-naive ALKþ NSCLC.
O1 6 1
Factors that affect distress faced by adolescents and young adults with cancer
Takatoshi Hirayama1, Hiroto Ishiki2, Yayoi Ando3, Ryoko Udagawa4, Mariko Kobayashi1,5, Rebekah Kojima2, Akie Shindo1, Moeko Tanaka1, Chiyuki Sasaki6, Saki Horiguchi6,7, Chiaki Kondo6, Kaori Sato6, Kazumi Ishii6, Emi Noguchi8, Ayako Mori6, Tatsuya Suzuki3, Ken Shimizu1, Eriko Satomi2 1 Department of Psycho-Oncology, National Cancer Center Hospital, Japan, 2 Department of Palliative Medicine, National Cancer Center Hospital, Japan, 3 Department of Hematology, National Cancer Center Hospital, Japan, 4Department of Pharmacy, National Cancer Center Hospital, Japan, 5Program of Clinical Psychology, Open University of Japan, 6Department of Nursing, National Cancer Center Hospital, Japan, 7National College of Nursing, Japan, 8Department of Breast and Medical Oncology, National Cancer Center Hospital, Japan Background: In our hospital, adolescent and young adult(AYA) inpatients are supported by a multidisciplinary care team using the data of screening sheet (SS) specially developed for AYA patients. The SS is made of two components; Distress Thermometer (DT) and a Problem list (PL). We conducted this study to explore the factors associated with distress of AYA patients by analyzing the data of the SS. Methods: The objects of this analysis were 67 SSs of the first hospitalization of each AYA inpatient aged 15-39 years between December 2017 and December 2018. We
doi:10.1093/annonc/mdz339 | vi83
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz339.006/5582971 by University of Cambridge user on 07 November 2019
(HR, 0.67; 95% CI, 0.32-1.41), and total pop (HR, 0.74; 95% CI, 0.38-1.42). ORR (PþC vs E): 50% vs 14% in CPS20, 32% vs 21% in CPS1, and 32% vs 31% in total pop; med DOR was 6.9 vs 2.6 mo, 7.5 vs 4.1 mo, and 7.5 vs 4.1 mo, respectively. Gr 3-5 TRAE rates (PþC vs E): 76% vs 90%. Conclusions: Responses were durable and safety was favorable in JPN pts, supporting P or PþC as 1L tx for R/M HNSCC. Tx with P or PþC improved PFS, OS, and ORR in JPN pts with CPS20. Although JPN pt numbers were small, data are consistent with those of the total study pop.
Annals of Oncology
O1 2 4
Efficacy of nivolumab for head and neck cancer arising from subsites which were not included in CheckMate 141
Yuri Ueda, Takao Fujisawa, Kazue Ito, Tomohiro Enokida, Susumu Okano, Makoto Tahara Department of Head and Neck Medical Oncology, National Cancer Center East, Japan Background: In the CheckMate 141 trial, nivolumab, a human IgG4 anti-PD-1 monoclonal antibody, provided a significant improvement in overall survival (OS) of patients with recurrent or metastatic squamous cell carcinoma (SCC) of the oral cavity, pharynx, or larynx. In Japan, nivolumab has been approved for platinum pretreated head and neck cancers regardless of histologic type and subsite. In other words, nivolumab is also available for non-SCC and subsites of head and neck cancer which were not included in the CheckMate 141 trial. However, the efficacy of nivolumab for cancers arising from these other subsites has not been clarified. Methods: We retrospectively reviewed data for 122 consecutive patients with head and neck cancers treated with nivolumab in our institution between March 2017 and December 2018. Patients with head and neck SCC of oral, oropharyngeal, hypopharyngeal, and laryngeal cancer were excluded. Final analysis of the study population was restricted to those 37 patients with non-SCC histological type or SCC arising from other subsites of the head and neck. Results: Median age was 57 years (range 30 to 77). Primary sites were nasopharynx/ sinonasal/salivary/other regions of the head and neck (n ¼ 8/10/8/11). Nineteen patients had SCC and 18 had non-SCC. In patients who could be evaluated by RECIST (n ¼ 32), objective response rate was 18.8% in the total study population, 37.5% in NPC, 10.0% in sinonasal cancer and 25.0% in salivary cancer. Median OS and time to treatment failure (TTF) in the total study population was 12.1 months and 2.3 months, respectively. Median TTF in NPC patients was better than that in patients with other primary sites (7.6 vs. 2.5 months, p ¼ 0.016). There was a trend toward improved TTF in SCC group compared to non-SCC group (4.2 vs. 2.4 months, p ¼ 0.31). Conclusion: Nivolumab showed favorable efficacy in head and neck cancers arising from subsites which were not included in the CheckMate141 trial, especially NPC patients.
O1 4 1
Effects of Dose Modifications on Safety and Efficacy of Dacomitinib for EGFR1 NSCLC in ARCHER 1050 Japanese Subset
Terufumi Kato1, Makoto Nishio2, Seiji Niho3, Noboru Yamamoto4, Toshiaki Takahashi5, Naoyuki Nogami6, Hiroyasu Kaneda7, Yuka Fujita8, Keith Wilner9, Mizuki Yoshida10, Mitsuhiro Isozaki10, Shinsuke Wada11, Fumito Tsuji12, Kazuhiko Nakagawa13 1 Kanagawa Cancer Center, Japan, 2The Cancer Institute Hospital of JFCR, 3National Cancer Center Hospital East, 4National Cancer Center Hospital, 5Shizuoka Cancer Center, 6Shikoku Cancer Center, 7Osaka City University, 8Asahikawa Medical Center, 9 Pfizer Oncology, 10Pfizer Research and Development Japan Biometrics and Data Management, 11Pfizer Research and Development Japan Clinical Research, 12SFJ Pharma Japan K.K, 13Kindai University Hospital Background: Dacomitinib (d) is effective first-line (1L) therapy in patients (pts) with EGFR-mutation-positive (EGFRþ) advanced NSCLC. In the ARCHER 1050 study (NCT01774721), 1L treatment with d was manageable and resulted in clinically meaningful, statistically significant improvement in PFS vs gefitinib (g). Here we present results for Japanese pts from ARCHER 1050. Methods: Pts with newly diagnosed stage IIIB/IV or recurrent EGFRþ advanced NSCLC were randomized to once-daily (qd) oral d 45 mg or g 250 mg. Randomization was stratified by race and EGFR mutation subtype. The primary endpoint was PFS. All pts enrolled were part of the efficacy analysis. Pts who received 1 dose of study drug were part of the safety analysis. Results: Of 452 total pts, 81 were Japanese; d (n ¼ 40), g (n ¼ 41). Median PFS was 18.2 mo for d (95% confidence interval [CI], 11.0-31.3) vs 9.3 mo for g (95% CI, 7.414.7). All 81 pts received study treatment. No grade (G) 4 or 5 adverse events (AEs) occurred in d-treated pts. Three G4 AEs (hepatic enzyme increases [n ¼ 2], suicide attempt) and a G5 AE (disease progression) occurred in g-treated pts. The most common G3 AEs were dermatitis acneiform (27.5%) and paronychia (22.5%) with d and ALT increased (12.2%) and abnormal hepatic function (7.3%) with g. Dose reduction occurred in 85% of d-treated pts; 24.4% of g-treated pts changed from qd to every other day dosing. Frequency and severity of special interest AEs (diarrhea, stomatitis, dermatitis and paronychia) were generally decreased after d dose reduction. Although the frequency of d dose modifications in Japanese pts was higher than in the ARCHER 1050 overall population, median treatment duration for pts who had d dose reductions was longer vs those who did not.
Volume 30 | Supplement 6 | October 2019
Conclusion: D significantly improved PFS over g in 1L treatment of Japanese pts with EGFRþ advanced NSCLC and had a manageable safety profile. Tolerability was improved and treatment duration was prolonged in pts who had their d dose reduced.
O1 4 2½Encore
Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK1 NSCLC from ALTA-1L
James CH Yang1, Hye R Kim2, Myung-Ju Ahn3, Ji-Youn Han4, Maximilian J Hochmair5, Ki H Lee6, Angelo Delmonte7, Maria R Garcia Campelo8, Dong-Wan Kim9, Enriqueta Felip10, Raffaele Califano11, Alexander Spira12, Scott Gettinger13, Marcello Tiseo14, Jeff Haney15, David Kerstein15, Sanjay Popat16, D R Camidge17 1 National Taiwan University Hospital, Taiwan, 2Yonsei University Severance Hospital, Seoul, South Korea, 3Samsung Medical Center, Seoul, South Korea, 4National Cancer Center, Goyang, South Korea, 5Department of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna, Austria, 6Chungbuk National University Hospital, Cheongju, South Korea, 7Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola, Italy, 8Complejo Hospitalario Universitario A Coruna Hospital Teresa Herrera-Materno Infantil, Coruna, Spain, 9Seoul National University Hospital, Seoul, South Korea, 10Vall d’Hebron University Hospital, Barcelona, Spain, 11The Christie NHS Foundation Trust, Manchester, England, United Kingdom, 12Virginia Cancer Specialists, Fairfax, VA, USA, 13Yale Cancer Center, New Haven, CT, USA, 14University Hospital of Parma, Parma, Italy, 15Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA, 16Royal Marsden Hospital, London, England, United Kingdom, 17University of Colorado Cancer Center, Aurora, CO, USA Background: We report results of the first interim analysis (IA) of BRG vs CRZ in ALK TKI-naive, ALKþ NSCLC from ALTA-1L (NCT02737501). Methods: This open-label, multicenter study enrolled pts with advanced ALKþ NSCLC who had 1 prior systemic therapy; asymptomatic CNS metastases were allowed. Pts were randomized 1:1 to BRG 180 mg QD with 7-day lead-in at 90 mg or CRZ 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed ORR, intracranial (i) ORR (iORR), and PFS (iPFS). IAs were planned at 50% and 75% of 198 expected PFS events. Results: 275 pts were randomized (BRG/CRZ, n ¼ 137/138); median age: 58/60 y. 26%/27% received prior chemotherapy for advanced disease; 29%/30% had baseline brain metastases. At data cutoff (19Feb2018), median follow-up of BRG/CRZ was 11.0/ 9.25 mo. With 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33-0.74, log-rank P¼0.0007); BRG median PFS (95% CI) was not reached (NR; NR) vs CRZ 9.8 months (9.0-12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30-0.68), log-rank P¼0.0001. Confirmed ORR for BRG was 71% (62-78) vs CRZ 60% (51-68). In pts with any iCNS disease (BRG/CRZ, n ¼ 43/47), confirmed iORR was 67% (51-81) vs 17% (831), P<0.0001. BRG median iPFS was NR (11 mo-NR) vs CRZ 6 mo (4-9); HR 0.27 (95% CI 0.13-0.54); log-rank P<0.0001. In pts with measurable iCNS disease (BRG/ CRZ, n ¼ 18/21), confirmed iORR was BRG 78% (52-94) vs CRZ 29% (11-52); P¼0.0028. Most common grade 3 TEAEs for BRG were increased CPK (16.2%) and lipase (13.2%), hypertension (9.6%), and for CRZ were increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis (BRG/CRZ): 3.7%/2.2%; discontinuations due to AE: 11.8%/8.8%. Conclusions: BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor-naive ALKþ NSCLC.
O1 6 1
Factors that affect distress faced by adolescents and young adults with cancer
Takatoshi Hirayama1, Hiroto Ishiki2, Yayoi Ando3, Ryoko Udagawa4, Mariko Kobayashi1,5, Rebekah Kojima2, Akie Shindo1, Moeko Tanaka1, Chiyuki Sasaki6, Saki Horiguchi6,7, Chiaki Kondo6, Kaori Sato6, Kazumi Ishii6, Emi Noguchi8, Ayako Mori6, Tatsuya Suzuki3, Ken Shimizu1, Eriko Satomi2 1 Department of Psycho-Oncology, National Cancer Center Hospital, Japan, 2 Department of Palliative Medicine, National Cancer Center Hospital, Japan, 3 Department of Hematology, National Cancer Center Hospital, Japan, 4Department of Pharmacy, National Cancer Center Hospital, Japan, 5Program of Clinical Psychology, Open University of Japan, 6Department of Nursing, National Cancer Center Hospital, Japan, 7National College of Nursing, Japan, 8Department of Breast and Medical Oncology, National Cancer Center Hospital, Japan Background: In our hospital, adolescent and young adult(AYA) inpatients are supported by a multidisciplinary care team using the data of screening sheet (SS) specially developed for AYA patients. The SS is made of two components; Distress Thermometer (DT) and a Problem list (PL). We conducted this study to explore the factors associated with distress of AYA patients by analyzing the data of the SS. Methods: The objects of this analysis were 67 SSs of the first hospitalization of each AYA inpatient aged 15-39 years between December 2017 and December 2018. We
doi:10.1093/annonc/mdz339 | vi83
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz339.006/5582971 by University of Cambridge user on 07 November 2019
(HR, 0.67; 95% CI, 0.32-1.41), and total pop (HR, 0.74; 95% CI, 0.38-1.42). ORR (PþC vs E): 50% vs 14% in CPS20, 32% vs 21% in CPS1, and 32% vs 31% in total pop; med DOR was 6.9 vs 2.6 mo, 7.5 vs 4.1 mo, and 7.5 vs 4.1 mo, respectively. Gr 3-5 TRAE rates (PþC vs E): 76% vs 90%. Conclusions: Responses were durable and safety was favorable in JPN pts, supporting P or PþC as 1L tx for R/M HNSCC. Tx with P or PþC improved PFS, OS, and ORR in JPN pts with CPS20. Although JPN pt numbers were small, data are consistent with those of the total study pop.