Supportive Care in Cancer

, Volume 25, Issue 1, pp 237–244 | Cite as

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits

  • L. J. Fallowfield
  • S. L. Catt
  • S. F. May
  • L. Matthews
  • V. M. Shilling
  • R. Simcock
  • S. Westwell
  • V. A. JenkinsEmail author
Original Article



The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies.

Patients and methods

As part of a longitudinal study Assessing the ‘VALue’ to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here.


Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists’ estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had ‘no idea’ or were ‘unclear’ what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment.


Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data.


Oncologists’ decision making Patients Metastatic cancer Progression-free survival estimates Therapeutic benefits 



We wish to thank all the patients who gave up their time to participate in the research, and also the oncologists, research nurses and trial co-ordinators. In addition, we would like to thank Angela Fry for her assistance with administration and Boehringer Ingelheim for the funds to conduct the study.

Compliance with ethical standards

Written consent was obtained prior to the initial interview, which took place within 2 weeks from the consultation with the doctor.

Conflict of interest

Lesley Fallowfield has received grant funding and speaker honoraria from Boehringer Ingelheim.

Supplementary material

520_2016_3408_MOESM1_ESM.pdf (152 kb)
ESM 1 (PDF 152 kb)


  1. 1.
    Booth CM, Eisenhauer AF (2012) Progression-free survival: meaningful or simply measurable? JCO 30(10):1030–1033CrossRefGoogle Scholar
  2. 2.
    National Cancer Institute website:, accessed August 10th 2016
  3. 3.
    Burzykowski T, Buyse M, Piccart-Gebhart MJ, et al. (2008) Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer. JCO 26(12):1987–1992CrossRefGoogle Scholar
  4. 4.
    Kim C, Prasad V (2015) Cancer drugs approved on the basis of a surrogate end point and subsequent overall survival: an analysis of 5 years of US food and drug administration approvals. JAMA Intern Med 175(12):1992–1994CrossRefPubMedGoogle Scholar
  5. 5.
    Prasad V, Kim C, Burotto M, et al. (2015) The strength of association between surrogate end points and survival in oncology: a systematic review of trial-level meta-analyses. JAMA Intern Med 175(8):1389–1398CrossRefPubMedGoogle Scholar
  6. 6.
    Fallowfield LJ, Fleissig A (2013) The value of progression-free survival to patients with advanced-stage cancer. Nat Rev Clin Onc 9(1):41–47CrossRefGoogle Scholar
  7. 7.
    Niraula S, Seruga B, Ocana A, et al. (2011) The price we pay for progress: a meta-analysis of harms of newly approved anticancer drugs. JCO 30(24):3012–3019CrossRefGoogle Scholar
  8. 8.
    Brundage MD, Feldman-Stewart D, Cosby R, et al. (2001) Cancer patients’ attitudes toward treatment options for advanced non-small cell lung cancer: implications for patient education and decision support. Pat Ed Counsel 45(2):149–157CrossRefGoogle Scholar
  9. 9.
    Bruner DW (2007) Should patient-reported outcomes be mandatory for toxicity reporting in cancer clinical trials? JCO 25(34):5345–5347CrossRefGoogle Scholar
  10. 10.
    Bridges JF, Mohamed AF, Finnern HW, et al. (2012) Patients’ preferences for treatment outcomes for advanced non-small cell lung cancer: a conjoint analysis. Lung Cancer 77(1):224–231CrossRefPubMedGoogle Scholar
  11. 11.
    Weeks JC, Cook EF, O’Day SJ, et al. (1998) Relationship between cancer patients’ predictions of prognosis and their treatment preferences. JAMA 279(21):1709–1714CrossRefPubMedGoogle Scholar
  12. 12.
    Jenkins V, Solis-Trapala I, Langridge C, et al. (2011) What oncologists believe they said and what patients believe they heard: an analysis of phase I trial discussions. JCO 29(1):61–68CrossRefGoogle Scholar
  13. 13.
    Temel JS, Greer JA, Admane S, et al. (2011) Longitudinal perceptions of prognosis and goals of therapy in patients with metastatic non-small-cell lung cancer: results of a randomized study of early palliative care. JCO 29(17):2319–2326CrossRefGoogle Scholar
  14. 14.
    Smith TJ, Hillner BE (2010) Explaining marginal benefits to patients, when ‘marginal’ means additional but not necessarily small. Clin Ca Res 16(24):5981–5986CrossRefGoogle Scholar
  15. 15.
    Christakis NA, Lamont EB (2000) Extent and determinants of error in doctors’ prognoses in terminally ill patients: prospective cohort study. BMJ 320:9–473CrossRefGoogle Scholar
  16. 16.
    Hodi FS, O’Day SJ, McDermott DF, et al. (2010) Improved survival with Ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Baselga J, Cortes J, Kim SB, et al. (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. NEJM 366:109–119CrossRefPubMedGoogle Scholar
  18. 18.
    Swain SM, Baselga J, Kim SB, et al. (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. NEJM 8:724–734CrossRefGoogle Scholar
  19. 19.
    Spicer J, Tischer B, Peters M. (2015) EGFR Mutation Testing and Oncologist Treatment Choice in Advanced NSCLC: Global Trends and Differences. Presented at ELCC abstract number LBA2_PRGoogle Scholar
  20. 20.
    Gelsomino F, Agustoni F, Niger M, et al. (2013) Epidermal growth factor receptor tyrosine kinase inhibitor treatment in patients with EGFR wild-type non–small-cell lung cancer: the never-ending story. JCO 31(26):3291–3293CrossRefGoogle Scholar
  21. 21.
    Chapman PB, Hauschild A, Robert C, et al. (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hauschild A, Grob JJ, Demidov LV, et al. (2012) Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380(9839):358–365CrossRefPubMedGoogle Scholar
  23. 23.
    NICE technology appraisal guidance [TA258] (2012) Erlotinib for first-line treatment of locally advanced or metastatic EGFR-TK positive non-small cell lung cancer. Accessed online 02/12/15 cancer N Engl J Med 366:109–119CrossRefGoogle Scholar
  24. 24.
    NICE technology appraisal guidance [TA162] (2008) Erlotinib for the treatment of non-small cell lung cancer. Accessed online 02/12/15Google Scholar
  25. 25.
    Hiu D, Sri Karuturi M, Tanco KC, et al. (2013) Targeted agent use in cancer patients at the end of life. J Pain Symptom Manag 46(1):1–8CrossRefGoogle Scholar
  26. 26.
    Ellis LM, Bernstein DS, Voest EE, et al. (2014) American Society of Clinical Oncology perspective: raising the bar for clinical trials by defining clinically meaningful outcomes. JCO 32(12):1186–1187CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • L. J. Fallowfield
    • 1
  • S. L. Catt
    • 1
  • S. F. May
    • 1
  • L. Matthews
    • 1
  • V. M. Shilling
    • 1
  • R. Simcock
    • 2
  • S. Westwell
    • 2
  • V. A. Jenkins
    • 1
    Email author
  1. 1.Sussex Health Outcomes Research & Education in Cancer (SHORE-C), Brighton and Sussex Medical SchoolUniversity of SussexBrightonUK
  2. 2.Sussex Cancer Centre Brighton and Sussex University Hospitals TrustBrightonUK

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