周一“星”视角|脏层胸膜侵犯对NSCLC复发的影响；劳拉替尼与克唑替尼治疗晚期ALK阳性非小细胞肺癌患者的比较

01

Nasser Altorki1, Xiaofei Wang2, Bryce Damman3, David R Jones4, Dennis Wigle5, Jeffrey Port1, Massimo Conti6, Ahmad S Ashrafi7, Moishe Lieberman8, Rodney Landreneau9, Kazuhiro Yasufuku10, Stephen Yang11, John D Mitchell12, Robert Keenan13, Thomas Bauer14, Daniel Miller15, David Kozono16, Jennifer Mentlick3, Everett Vokes17, Thomas E Stinchcombe18

1 Weill Cornell Medicine, New York-Presbyterian Hospital, New York.

2 Alliance Statistics and Data Management Center, and Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

3 Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota.

4 Memorial Sloan Kettering Cancer Center, New York, New York.

5 Mayo Clinic, Rochester, Minnesota.

6 Institut Universitaire de Cardiologie et Pneumologie de Québec, Quebec , Canada.

7 Surrey Memorial Hospital Thoracic Group Fraser Valley Health Authority, British Columbia, Canada.

8 Centre Hospitalier de l'Université de Montréal, Montreal, Québec, Canada.

9 Tampa General Hospital, Tampa, Florida.

10 University of Toronto, Toronto, Ontario, Canada.

11 Johns Hopkins University, Baltimore, Maryland.

12 University of Colorado Hospital School of Medicine, Aurora.

13 Moffitt Cancer Center, Tampa, Florida.

14 Hackensack Meridian Health System, Edison, New Jersey.

15 Medical College of Georgia, Augusta.

16 Alliance Protocol Operations Office, Boston, Massachusetts.

17 University of Chicago Comprehensive Cancer Center, Chicago, Illinois.

18 Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Importance: 

The randomized clinical trial Cancer and Leukemia Group B (CALGB) 140503 showed that for patients with clinically staged T1N0 non–small cell lung cancer (NSCLC; ≤2 cm), sublobar resections were associated with similar oncological outcomes to those after lobar resection. The association of the extent of parenchymal resection with recurrence and survival in patients with tumors pathologically upstaged to T2 based on visceral pleural invasion (VPI) is controversial.

Objective: 

To determine survival and recurrence rates in patients with small peripheral pT2 NSCLC (≤2 cm) that was treated by either lobar or sublobar resection in CALGB 140503.

Design, Participants, and setting: 

CALGB 140503, a randomized multicenter noninferiority trial, included 697 patients with small peripheral NSCLC that was clinically staged as T1N0. Enrollment was from June 2007 through March 2017 at 83 participating institutions, and after a median follow-up of 7 years, the primary outcome of disease-free survival after sublobar resection was noninferior to that after lobar resection.

Intervention:

 Lobar or sublobar resection.

Main outcomes and measures: 

Survival end points were estimated by the Kaplan-Meier estimator. Hazard ratios and 95% CIs were estimated using stratified Cox proportional hazard models.

Results: 

Of 679 participants, 390 (57.4%) were female, and the median (range) age was 67.8 (37.8-89.7) years. Among 697 patients randomized, 566 (81.2%) had pT1 tumors (no VPI) and 113 (16.2%) had pT2 tumors (VPI). Five-year disease-free survival was 65.9% (95% CI, 61.9%-70.2%) in patients with pT1 compared with 53.3% (95% CI, 44.3%-64.1%) in patients with pT2 tumors (stratified log-rank: P = 0.02). Disease recurrence developed in 27.6% of patients with pT1 (locoregional only: 60 [10.8%]; distant only: 81 [14.6%]) and 41.6% of those with pT2 (locoregional only: 17 [15.0%]; distant only: 27 [23.9%]). Five-year recurrence-free survival was 73.1% (95% CI, 69.2%-77.1%) for pT1 tumors and 58.2% (95% CI, 49.2%-68.8%) for pT2 tumors (stratified log-rank: P = 0.01). There were no intergroup differences in disease-free or recurrence-free survival based on the extent of parenchymal resection.

Conclusions and relevance: 

The results of this secondary analysis suggest that compared with patients with tumors without VPI, patients who had tumors with VPI had worse disease-free and recurrence-free survival and a higher rate of local and distant disease recurrence. These high rates of recurrence were independent of the extent of parenchymal resection, and these data support the inclusion of these patients in adjuvant therapy trials.

[CITATION]: Altorki N, Wang X, Damman B, et al. Recurrence of Non-Small Cell Lung Cancer With Visceral Pleural Invasion: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2024 Aug 1:e242491.

[DOI]: 10.1001/jamaoncol.2024.2491.

[IF]: 22.5

02

Benjamin J Solomon1 , Geoffrey Liu2, Enriqueta Felip3, Tony S K Mok4, Ross A Soo5, Julien Mazieres6, Alice T Shaw7, Filippo de Marinis8, Yasushi Goto9, Yi-Long Wu10, Dong-Wan Kim11, Jean-François Martini12, Rossella Messina13, Jolanda Paolini13, Anna Polli13, Despina Thomaidou13, Francesca Toffalorio13, Todd M Bauer14

1 Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 

2 Princess Margaret Cancer Centre, Toronto, ON, Canada. 

3 Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 

4 State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, China. 

5 National University Cancer Institute, Singapore. 

6 Pulmonology Department, Toulouse University Hospital and Centre de Recherche Cancerologie Toulouse CRCT, INSERM, France. 

7 Massachusetts General Hospital Cancer Center, Boston, MA. 

8 Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy. 

9 Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 

10 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangdong, China. 

11 Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. 

12 Pfizer, La Jolla, CA. 

13 Pfizer, Milan, Italy. 

14 Greco-Hainsworth Centers for Research/Tennessee Oncology, Nashville, TN.

Purpose: 

Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, ALK-positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up.

Methods:

Two hundred ninety-six patients with ALK-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.

Results: 

With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new ALK resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment.

Conclusion: 

After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer.

[CITATION]: Benjamin J Solomon, Geoffrey Liu , Enriqueta Felip , et al. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non–Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol. 2024 May 31:JCO2400581.

[DOI]:10.1200/JCO.24.00581.

[IF]: 42.1