Special issue "The advance of solid tumor research in China": Real-world clinical outcomes of alectinib for advanced non-small-cell lung cancer patients with ALK fusion in China.

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced non-small-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that "crizotinib pretreatment", "liver metastasis", and "TP53 co-mutation" were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice. READ ARTICLE

Int J Cancer DOI:10.1002/ijc.34123

Authors: Su C, Zhou J, Qiang H, Zhao J, Chang Q, Ji X, Li J, Xie M, Chu T.

Association of anticoagulant use with clinical outcomes from crizotinib in ALK- and ROS1-rearranged advanced non-small cell lung cancers: A retrospective analysis of PROFILE 1001

Background: ROS1- and ALK-rearranged advanced NSCLCs are associated with increased thromboembolic risk. We hypothesized that a prothrombotic phenotype offers an evolutionary advantage to subsets of these cancers. The impact of this phenotype could alter outcomes from targeted therapy.

Methods: In a retrospective analysis of ROS1- and ALK-rearranged NSCLCs treated with crizotinib in a phase 1 trial, we compared progression-free survival (PFS) and objective response rate (ORR) based on the history of anticoagulation use (a possible surrogate of thromboembolism) at baseline (within 90 days before study enrollment) or within 90 days of study treatment.

Results: Twelve out of 53 (22.6%) ROS1- and 39 out of 153 (25.5%) ALK-rearranged NSCLCs received anticoagulation before or during the trial. Most ROS1 and ALK patients on anticoagulation received low-molecular-weight heparin (75% and 64.1%, respectively). In the ROS1-rearranged group, the median PFS (95% CI) values were 5.1 (4.4-14.4) and 29.0 (16.5-48.8) months, and the ORR values were 41.7% (95% CI: 15.2 to 72.3) and 80.5% (95% CI: 65.1 to 91.2) among those with and without anticoagulation treatment, respectively. In the ALK-rearranged group, the median PFS (95% CI) was 7.1 (5.4-7.7) and 12.0 (9.4-18.3) months, and the ORR was 41% (95% CI: 25.6 to 57.9) and 74.3% (95% CI: 65.3 to 82.1) among those with and without anticoagulation, respectively.

Conclusions: Anticoagulation (as a potential surrogate of a prothrombotic subset) in ROS1- and ALK-rearranged NSCLCs may be associated with a lower PFS and ORR to crizotinib. READ ARTICLE

Cancer Medicine DOI:10.1002/cam4.4789.

Authors: Ng TL, Tsui DCC, Wang S, Usari T, Patil T, Wilner K, Camidge DR.

Clinical TrialsKirk SmithMay 5, 2022ALK, ROS1, crizotinib, lung cancer, thromboembolism

Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial

Introduction: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ NSCLC. Methods: Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into {less than or equal to}median and >median cfDNA biomarker-evaluable populations (BEP). Effect of cfDNA concentration on outcomes was analyzed using a Cox regression model with treatment group as covariate, and in multivariate analyses. Results: Median cfDNA concentration in the BEP was 11.53 ng/mL (n = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all p<0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the {less than or equal to}median BEP (alectinib adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI): 1.07-3.89], p=0.0305; crizotinib adjusted HR 1.83 [95% CI: 1.11-3.00], p=0.0169). Median progression-free survival was longer with alectinib than crizotinib in both {less than or equal to}median and >median BEPs (p<0.0001). Overall survival data remain immature; survival probability was lower in the >median versus {less than or equal to}median BEP in both treatment arms (alectinib HR 2.52 [95% CI: 1.08-5.88], p=0.0333; crizotinib HR 2.63 [95% CI: 1.27-5.47], p=0.0096). Conclusion: These data suggest that plasma cfDNA concentration may have prognostic value in advanced ALK+ NSCLC. Prospectively designed studies are warranted to investigate this finding. READ ARTICLE

Clinical Cancer Research DOI:10.1158/1078-0432.CCR-21-2840

Authors: Rafal Dziadziuszko, Solange Peters, Tony Mok, D. Ross. Camidge, Shirish M. Gadgeel, Sai-Hong Ignatius. Ou, Krzysztof Konopa, Johannes Noé, Malgorzata Nowicka, Walter Bordogna, Peter N. Morcos, Vlatka Smoljanovic, Alice T. Shaw

Clinical TrialsKirk SmithFebruary 23, 2022Chemotherapy, targeted therapy, imaging, chest, lung cancer

Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial

WX-0593 (Iruplinalkib) is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor (TKI). In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer (NSCLC) patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety assessed by investigators. In the dose-expansion phase, the primary endpoint was objective response rate (ORR) assessed by investigators. Between September 25, 2017 and October 15, 2018, a total of 153 patients received WX-0593 treatment. Two dose-limiting toxicities (DLTs) including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient. MTD was not rea..... READ ARTICLE

Signal Transduction and Targeted Therapy DOI:10.1038/s41392-021-00841-8

Authors: Shi, Y., Fang, J., Hao, X. et al.

Continuation of Lorlatinib in ALK-positive NSCLC Beyond Progressive Disease

Continuing LBPD is a viable treatment option for select patients with ALK-positive NSCLC who progressed on lorlatinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.12.011

Authors: Sai-Hong I.Ou, Benjamin J.Solomon, Alice T.Shaw, Shirish M.Gadgeel, BenjaminBesse, Ross A.Soo, Antonello Abbattista, Francesca Toffalorio, Robin Wiltshire, Alessandra Bearz

Clinical TrialsKirk SmithJanuary 10, 2022lorlatinib, NSCLC, post-progression treatment, RECIST 1.1

Short communication: The activity of brigatinib in patients with disease progression after next generation anaplastic lymphoma tyrosine kinase inhibitors...

Highlights:
- Brigatinib demonstrated activity in patients with disease progression after next-generation anaplastic lymphoma (ALK) tyrosine kinase inhibitors (TKI’s).
- The objective response was similar in patients who received next generation ALK inhibitors as first-line or second line therapy, and patients with and without brain metastases at baseline.
- Circulating tumor DNA testing (ctDNA) for ALK resistance mutations is feasible; however, a number of patients did not have detectable ctDNA or an ALK resistance mutations. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.12.019

Authors: Thomas E. Stinchcombe, Xiaofei Wang, Robert C. Doebele, Leylah M. Drusbosky, David E. Gerber, Leora Horn, Erin M. Bertino, Geoff Liu, Liza C. Villaruz, D. Ross Camidge

Clinical TrialsKirk SmithJanuary 3, 2022Targeted therapy, biomarker, ctDNA, liquid biopsy

Genetic landscape of patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study

NGS data were generated for 85 pts (ALKi-pretreated [n = 54]; ALKi-naïve [n = 31]), 57 were collected from patients before exposure to any ALKi. NGS did not detect ALK rearrangement in 14 of 85 patients; several of these ALK NGS negative cases harbored alternative drivers, e.g. EGFR mutation. Of the 71 biopsies with NGS confirmed ALK rearrangement, the most frequently detected rearrangements were EML4-ALK variant 1 (V1) and EML4-ALK V3 (36.6% [26/71] and 32.4% [23/71] respectively). Eight (six crizotinib-pretreated and two pretreated with crizotinib followed by alectinib) of the 21 ALKi-pretreated patients carried a point mutation of the ALK TKD, and had the biopsy collected between 1 and 14 days before ceritinib; with the exception of one patient with a G1202R point mutation, all patients derived clinical benefit from ceritinib treatment.
Of the 14 ALKi-naïve patients, ceritinib was effective in almost all patients, including a patient carrying a concomitant ERBB4 and HGF amplificatio..... READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.11.007

Authors: D.S-W.Tana, M.Thomas, DW.Kim, S. Szpakowski, P. Urban, R. Mehra, L.Q.M. Chow, S. Sharma, B.J. Solomon, E.Felip, D.R. Camidge, J. Vansteenkiste, L. Petruzzelli, S. Pantano and A.T. Shaw

CD30-Directed Chimeric Antigen Receptor (CAR)-T Cells for Treatment of Hodgkin Lymphoma and Non-Hodgkin Lymphoma in Pediatric Patients

Chimeric antigen receptor (CAR)-T cell therapy targeting the CD19 antigen has been effective in treating B-cell acute lymphoblastic leukemia. As CAR-T cells targeting new antigens are being explored for the treatment of other cancers in adults, parallel studies are warranted for pediatric cohorts. We have previously shown the safety and efficacy in adults of CAR-T cells targeting CD30, which is expressed in classical Hodgkin Lymphoma (HL) and in some Non-Hodgkin Lymphoma (NHL). We have therefore sought to study the feasibility and the safety of CD30.CAR-T cells in pediatric patients with relapsed/refractory CD30-expressing HL and Anaplastic Large Cell Lymphoma (ALCL). READ ARTICLE

Blood DOI:10.1182/blood-2021-153968

Authors: George E.Hucks Jr., Barbara Savoldo, Gianpietro Dotti, Catherine Joyce, Arago Cheng, Caroline Babinec, Kimberly A.Kasow, Michael Winstead, Arpita Patel, Cammie Presler, Natalie SGrover, J. Kaitlin Morrison, Anne W.Beaven, Marcie L.Riches, Thomas C.Shea, Jonathan S.Serody

Safety and activity of alectinib plus bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer: a phase I/II study

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is highly effective in advanced ALK-rearranged non-small-cell lung cancer and represents a standard first-line therapy. New strategies are needed, however, to delay resistance. We conducted a phase I/II study to assess the safety and efficacy of combining alectinib with bevacizumab, a monoclonal antibody against vascular endothelial growth factor.
Patients with advanced ALK-rearranged non-squamous non-small-cell lung cancer were enrolled. The phase I portion employed a dose de-escalation strategy with alectinib and bevacizumab starting at the individual standard doses. The primary objective was to determine the recommended phase II dose (RP2D). In phase II, the primary objective was to evaluate the safety of the combination at the RP2D; the secondary objective was to determine extracranial and intracranial efficacy.
Eleven patients were enrolled between September 2015 and February 2020. Mos..... READ ARTICLE

ESMO Open, Cancer Horizons DOI:10.1016/j.esmoop.2021.100342

Authors: J.J. Lin, A. Muzikansky, E. Kennedy, I. Dagogo-Jack, A.T. Shaw, J.F. Gainor

Blood First Assay Screening Trial (BFAST) in Treatment-Naive Advanced or Metastatic NSCLC: Initial Results of the Phase 2 ALK-Positive Cohort

Introduction: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. Conclusions: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.07.008

Authors: Rafal Dziadziuszko, Tony Mok, Solange Peters, Ji-Youn Han, Jorge Alatorre-Alexander,
Natasha Leighl, Virote Sriuranpong, Maurice Pérol, Gilberto de Castro Junior, Ernest Nadal, Filippo de Marinis, Osvaldo Arén Frontera, Daniel S.W. Tan, Dae Ho Lee, Hye Ryun Kim, Mark Yan, Todd Riehl, Erica Schleifman, Sarah M. Paul, Simonetta Mocci, Rajesh Patel, Zoe June Assaf, David S. Shames, Michael S. Mathisen, Shirish M. Gadgeel

Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial

Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee–assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35–0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53–1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21–0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superi..... READ ARTICLE

Journal of Thoracic Oncology
DOI:10.1016/j.jtho.2021.07.035

Authors: D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James C.H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Maria Rosario, Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Scott N. Gettinger, Marcello Tiseo, Huamao M. Lin, Yuyin Liu, Florin Vranceanu, Huifeng Niu, Pingkuan Zhang and Sanjay Popat

The Effect of a High-Fat Meal on the Pharmacokinetics of Brigatinib, an Oral Anaplastic Lymphoma Kinase Inhibitor, in Healthy Volunteers

Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, received accelerated approval in the United States for the treatment of patients with metastatic ALK+ non–small-cell lung cancer who have progressed on or are intolerant to crizotinib. A clinical study was conducted to assess the effect of food on brigatinib pharmacokinetics (PK). Healthy subjects received a single oral dose of brigatinib 180 mg (2 × 90-mg tablets) after a 10-hour fast or after a high-fat meal in a 2-period, 2-sequence crossover study. Plasma samples for PK characterization were collected over 168 hours postdose. Twenty-four subjects were enrolled (mean age 44 years; 58% male), with 21 included in the PK-evaluable population. Brigatinib peak concentration was reduced by 13% under fed (high-fat meal) versus fasted conditions, with no effect on area under the concentration-time curve. The median time to peak concentration of brigatinib was longer under fed conditions (5 hours) than in fasted condit..... READ ARTICLE

Clinical Pharmacology in Drug Development
DOI:10.1002/cpdd.641

Authors: Meera Tugnait,Neeraj Gupta,Michael J. Hanley,Karthik Venkatakrishnan,Daryl Sonnichsen,David Kerstein,David J. Dorer,Narayana Narasimhan

Genetic landscape of patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study

Objectives: To better understand genetic determinants of response to ceritinib, an exploratory analysis was conducted using tumor biopsies from anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients treated with ceritinib at doses of ≥ 300 mg in the ASCEND-1 study. Conclusions: This exploratory analysis highlights the potential role of NGS in improving our understanding of response and resistance to ceritinib. It also illustrates that ceritinib is active against almost all ALK resistance mutations found in ALKi-pretreated patients. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.11.007

Authors: D S-W Tan, M Thomas, D-W Kim, S Szpakowski, P Urban, R Mehra, L Q M Chow, S Sharma, B J Solomon, E Felip, D R Camidge, J Vansteenkiste, L Petruzzelli, S Pantano, A T Shaw

Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

How robust are conclusions about the comparative effectiveness of the ALK inhibitor alectinib vs ceritinib in crizotinib-refractory, ALK-positive non–small cell lung cancer from indirect comparisons using real-world data (RWD)? This comparative effectiveness study including 355 patients found that alectinib exposure was associated with improved survival compared with ceritinib in both single-group trials and multicenter US RWD. Results were robust to a range of plausible assumptions about unmeasured confounding and missing Eastern Cooperative Oncology Group Performance Status and underrecorded comorbidities in RWD. Alectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC, and only substantial levels of bias examined reversed the findings. These findings suggest that quantitative bias analysis can be a useful tool to address uncertainty of findings for decision-makers considering RWD. READ ARTICLE

JAMA Network Open DOI:10.1001/jamanetworkopen.2021.26306

Authors: Wilkinson S, Gupta A, Scheuer N, Mackay E, Arora P, Thorlund K, Wasiak R, Ray J, Ramagopalan S, Subbiah V.

Clinical Trials, group2Kirk SmithOctober 1, 2021Alectinib, Ceritinib, Non–Small Cell Lung Cancer, Trials

Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase−Positive Non–Small Cell Lung Cancer, A Randomized Clinical Trial

Question Is ensartinib superior to crizotinib for patients with advanced anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) who have not been treated previously with an ALK inhibitor?
Findings This randomized clinical phase 3 trial including 290 patients met the primary end point; the median progression-free survival was statistically significantly longer with ensartinib than with crizotinib (25.8 vs 12.7 months), and the confirmed intracranial response rate was 64% with ensartinib vs 21% with crizotinib for patients with brain metastases at baseline. Ensartinib had a favorable safety profile.
Meaning Ensartinib represents a new first-line treatment option for patients with ALK-positive NSCLC. READ ARTICLE

JAMA Oncology DOI:10.1001/jamaoncol.2021.3523

Authors: Leora Horn, Ziping Wang, Gang Wu, Elena Poddubskaya, Tony Mok, Martin Reck, Heather Wakelee, Alberto A. Chiappori, Dae Ho Lee, Valeriy Breder, Sergey Orlov, Irfan Cicin, Ying Cheng, Yunpeng Liu, Yun Fan, Jennifer G. Whisenant, Yi Zhou, Vance Oertel, Kim Harrow, Chris Liang, Li Mao, Giovanni Selvaggi and Yi-Long Wu,

Clinical Trials, group3Kirk SmithSeptember 2, 2021ALK, Ensartinib, eXalt3 trial, non-small cell lung cancer (NSCLC)

Brigatinib versus Crizotinib in Anaplastic Lymphoma Kinase (ALK) Inhibitor–Naive Advanced ALK-Positive Non–Small Cell Lung Cancer: Final Results of the Phase 3 ALTA-1L Trial

In the phase 3 ALTA-1L study of brigatinib in anaplastic lymphoma kinase (ALK) inhibitor–naive advanced ALK+ NSCLC, brigatinib demonstrated superior progression-free survival (PFS) versus crizotinib in 2 planned interim analyses. We report final efficacy, safety, and exploratory results. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.07.035

Authors: D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James CH. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Maria Rosario Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Scott N. Gettinger, Marcello Tiseo, Huamao M. Lin, Yuyin Liu, Florin Vranceanu, Huifeng Niu, Pingkuan Zhang, Sanjay Popat

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non–Small Cell Lung Cancer

In this randomized clinical trial, the addition of metformin to concurrent chemoradiation was well tolerated but did not improve survival among patients with unresectable stage III NSCLC. ClinicalTrials.gov Identifier: NCT02186847 READ ARTICLE

JAMA: Journal of American Medical Association DOI:10.1001/jamaoncol.2021.2318

Authors: Heath Skinner, MD,PhD; Chen Hu, PhD; Theodoros Tsakiridis, MD, PhD; Rafael Santana-Davila, MD; Bo Lu, MD; Jeremy J. Erasmus, MD; Anthony J. Doemer, MS; Gregory M. M. Videtic, MD; James Coster, MD; Alex Xuezhong Yang, MD; Richard Y. Lee, MD, PhD; Maria Werner-Wasik, MD; Philip E. Schaner, MD, PhD; Steven E. McCormack, MD; Benjamin T. Esparaz, MD; Ronald C. McGarry, MD,PhD; Jose Bazan, MD; Timothy Struve, MD; Rebecca Paulus, BS and Jeffrey D. Bradley, MD

Clinical Trials, group4Kirk SmithJuly 29, 2021NSCLC, metformin, chemoradiation

Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer

Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS). We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features. READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.14083

Authors: Donghui Hou, Xiaomin Zheng, Wei Song, Xiaoqing Liu, Sicong Wang, Lina Zhou, Xiuli Tao, Lv Lv, Qi Sun, Yujing Jin,Zewei Zhang, Lieming Ding, Ning Wu, Shijun Zhao

Brigatinib in Japanese patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC): First results from the J-ALTA

Background: Brigatinib is a next-generation ALK inhibitor with demonstrated activity against ALK mutations. We report primary analysis results with brigatinib in Japanese patients with ALK-positive NSCLC who have not previously been treated with an ALK TKI in the phase 2 J-ALTA study (NCT03410108). Conclusions: In the J-ALTA TKI-naive cohort, brigatinib demonstrated substantial efficacy and manageable safety in the Japanese patient population. Brigatinib remains one of the treatment options in Japanese patients. Clinical trial information: NCT03410108. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2021.39.15_suppl.9042

Authors: Masashi Kondo, Shunichi Sugawara, Toshihide Yokoyama, Toru Kumagai, Makoto Nishio, Koichi Goto, Yuichiro Ohe, Takashi Seto, Nobuyuki Yamamoto, Kentarou Kudou, Takayuki Asato, Pingkuan Zhang, Kazuhiko Nakagawa

Genetic Analysis and Operative Outcomes in Patients with Oncogene-Driven Advanced NSCLC Treated with Cytoreductive Surgery as a Component of Local Consolidative Therapy

Most patients with oncogene-driven advanced non-small cell lung cancer (NSCLC) demonstrate recurrence because of the developing targeted therapy resistance. In this retrospective study, we assessed the efficacy of surgical local consolidative treatment by analyzing the operative outcomes and genetic data in 44 patients who underwent pulmonary resection for stage IIIB/C-IV NSCLC after targeted therapy. The initial mutations were in the EGFR (n = 32), ALK (n = 11), and ROS1 (n = 1) genes. The median interval from the initiation of tyrosine kinase inhibitor (TKI) therapy immediately before the surgery to the actual operation was 9.8 months. Operative mortality was absent. Four patients showed complete remission. The median follow-up period after TKI therapy initiation was 23.1 months. The Kaplan-Meier survival analysis showed that the 2-year failure-free survival and overall survival rates from the initiation of TKI were 70.8% and 95.0%, respectively. During the follow-up period, two patients died and 15 suffered from disease progression. Among the 32 patients with EGFR mutations, 12 showed additional mutations, and targeted agents were replaced in nine patients after the operation. We conclude that pulmonary resection for advanced NSCLC after targeted therapy is feasible, and the surgical specimens could be used for planning further targeted therapy. READ ARTICLE

Cancers DOI: 10.3390/cancers13112549

Authors: Byung Jo Park , Hyo Sup Shim , Chang Young Lee , Jin Gu Lee , Hye Ryun Kim , Sang Hoon Lee , Min Hee Hong and Seong Yong Park