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Real-world outcomes according to treatment strategies in ALK-rearranged non-small-cell lung cancer (NSCLC) patients: an Italian retrospective study

  • E. GobbiniEmail author
  • R. Chiari
  • P. Pizzutillo
  • P. Bordi
  • L. Ghilardi
  • S. Pilotto
  • G. Osman
  • F. Cappuzzo
  • F. Cecere
  • F. Riccardi
  • V. Scotti
  • O. Martelli
  • G. Borra
  • E. Maiello
  • A. Rossi
  • P. Graziano
  • V. Gregorc
  • C. Casartelli
  • C. Sergi
  • A. Del Conte
  • A. Delmonte
  • C. Bareggi
  • D. Cortinovis
  • P. Rizzo
  • F. Tabbò
  • G. Rossi
  • E. Bria
  • D. Galetta
  • M. Tiseo
  • M. Di Maio
  • S. Novello
Research Article

Abstract

Purpose

Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received.

Patients

We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions.

Results

After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9–11.2] and 11.1 months [CI 95% 9.2–13.8], respectively, while TTF were 10.2 [CI 95% 8.5–12.6] and 11.9 months [CI 95% 9.7–17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3–33.7] in PFS and 30.4 months [CI 95% 24.7–34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8–54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0–73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6–NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3–34.0)] (P < 0.0001).

Conclusion

The sequential administration of crizotinib and a new generation ALKis provided a remarkable clinical benefit in this real-life population, being an interesting option to consider in selected patients.

Keywords

Lung cancer ALK inhibitors Sequence 

Notes

Authors contribution

S. Novello, M. Di Maio, M. Tiseo, P. Graziano, D. Galetta, E. Bria, A. Rossi and G. Rossi contributed to the study conception and design. Material preparation, data collection and analysis were performed by E. Gobbini with the contribution of all other authors. The first draft of the manuscript was written by E. Gobbini and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

Dr. Gobbini reports personal fees from Astrazeneca, grants and personal fees from Bristol-Myers Squibb, personal fees from Roche, personal fees from Merck Sharpe and Dohme, outside the submitted work; Dr. Pilotto reports personal fees from Astrazeneca, personal fees from Eli-Lilly, personal fees from Bristol Mayers Squibb, personal fees from Boehringer Ingelheim, personal fees from Roche, personal fees from Merck Sharpe and Dohme, personal fees from Istituto Gentili, outside the submitted work; Dr. Scotti reports personal fees from Roche, personal fees from Pfizer, outside the submitted work; Dr. Rossi reports personal fees from Roche, outside the submitted work; Dr. Cappuzzo reports personal fees from Roche, personal fees from Astrazeneca, personal fees from Brystol Myers Squibb, personal fees from Takeda, personal fees from Pfizer, personal fees from Eli-Lilly, personal fees from Merck Sharpe and Dohme, outside the submitted work; Dr. Di Maio reports personal fees from Brystol Myers Squibb, personal fees from Merck Sharp and Dohme, personal fees from Roche, personal fees from Astrazeneca, personal fees from Janssen, personal fees from Takeda, personal fees from Pfizer, outside the submitted work; Dr. Tiseo reports personal fees from Astrazeneca, personal fees from Brystol Myers Squibb, personal fees from Merck Sharpe and Dohme, personal fees from Boehringer Ingelheim, from Takeda, outside the submitted work; Dr. Novello reports personal fees from Astrazeneca, personal fees from Boheringer Ingelheim, personal fees from Brystol Myers Squibb, personal fees from Celgene, personal fees from Eli-Lilly, personal fees from Abbvie, personal fees from Merck Sharpe and Dohme, personal fees from Takeda, personal fees from Pfizer, personal fees from Roche, outside the submitted work.

Ethical approval

All procedures performed in this retrospective study involving human participants were in accordance with the ethical standards of the oncologic centers involved. Notably, this study (protocol n° 11/663) was approved by the central institutional review board of San Luigi Hospital in Orbassano (reference n° 91/2014) and the decision was transmitted to all the other oncologic centers involved.

Informed consent

Informed consent was obtained from all individual participants included in the study for retrieving data from hospital medical record systems. Anonymized data were thus collected at the San Luigi Hospital. This protocol did not modify patient’s clinical management.

Supplementary material

12094_2019_2222_MOESM1_ESM.docx (199 kb)
Supplementary file1 (DOCX 199 kb)

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  • E. Gobbini
    • 1
    • 2
    Email author
  • R. Chiari
    • 3
  • P. Pizzutillo
    • 4
  • P. Bordi
    • 5
  • L. Ghilardi
    • 6
  • S. Pilotto
    • 7
  • G. Osman
    • 8
  • F. Cappuzzo
    • 9
  • F. Cecere
    • 10
  • F. Riccardi
    • 11
  • V. Scotti
    • 12
  • O. Martelli
    • 13
  • G. Borra
    • 14
  • E. Maiello
    • 15
  • A. Rossi
    • 15
  • P. Graziano
    • 15
  • V. Gregorc
    • 16
  • C. Casartelli
    • 17
  • C. Sergi
    • 18
  • A. Del Conte
    • 19
  • A. Delmonte
    • 20
  • C. Bareggi
    • 21
  • D. Cortinovis
    • 22
  • P. Rizzo
    • 23
  • F. Tabbò
    • 1
  • G. Rossi
    • 24
  • E. Bria
    • 25
  • D. Galetta
    • 4
  • M. Tiseo
    • 5
  • M. Di Maio
    • 26
  • S. Novello
    • 1
  1. 1.Department of OncologyUniversity of Turin, San Luigi Gonzaga HospitalOrbassanoItaly
  2. 2.Cancer Research Center Lyon, Centre Léon BérardLyon Cedex 08France
  3. 3.Oncology UnitSanta Maria della Misericordia HospitalPerugiaItaly
  4. 4.Medical Thoracic UnitIRCCS Istituto Oncologico “Giovanni Paolo II”BariItaly
  5. 5.Medical Oncology UnitUniversity HospitalParmaItaly
  6. 6.Oncology DepartmentPapa Giovanni XXIII HospitalBergamoItaly
  7. 7.Oncology Unit, Department of MedicineUniversity of VeronaVeronaItaly
  8. 8.UOSD Pneumologia Oncologica, San Camillo Forlanini HospitalRomaItaly
  9. 9.Oncology and Hematology DepartmentAUSL Romagna-RavennaRavennaItaly
  10. 10.Regina Elena National Cancer InstituteRomaItaly
  11. 11.Oncology UnitAntonio Cardarelli HospitalNapoliItaly
  12. 12.Radiotherapy UnitUniversity Hospital CareggiFirenzeItaly
  13. 13.Medical Oncology UnitSan Giovanni Addolorata HospitalRomeItaly
  14. 14.Oncology UnitEast Piedmont UniversityNovaraItaly
  15. 15.Department of Oncology and HematologyFoundation IRCCS ‘Casa Sollievo della Sofferenza’San Giovanni RotondoItaly
  16. 16.Department of Medical OncologyIstituto di Ricovero e Cura a Carattere Scientifico, San Raffaele HospitalMilanoItaly
  17. 17.Oncology UnitValduce HospitalComoItaly
  18. 18.Oncology UnitA.O.R.N.A.S Garibaldi NesimaCataniaItaly
  19. 19.S.O.C. Oncologia Medica e dei Tumori Immunocorrelati, Centro di Riferimento Oncologico (CRO), IRCCSAvianoItaly
  20. 20.Thoracic Oncology GroupIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCSMeldolaItaly
  21. 21.Oncology UnitFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  22. 22.Oncology UnitASST San Gerardo HospitalMonzaItaly
  23. 23.Medical Oncology Division and Breast UnitAntonio Perrino HospitalBrindisiItaly
  24. 24.Operative Unit of Pathologic Anatomy, Azienda Unità Sanitaria Locale della Romagna, Hospital St. Maria delle CrociRavennaItaly
  25. 25.U.O.C. Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro CuoreRomaItaly
  26. 26.Department of OncologyUniversity of TurinTurinItaly

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