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An appraisal of FDA approvals for adult solid tumours in 2017–2021: has the eagle landed?

Nature Reviews Clinical Oncology volume 19, pages 486–492 (2022)Cite this article

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Abstract

In 2016, the then US President Barack Obama announced the Cancer Moonshot with a view to making 10 years’ worth of progress in cancer prevention, diagnosis and treatment in only 5 years. This Perspective evaluates the FDA approvals of therapeutic agents for use in solid tumour oncology for the period 2017–2021 against the aspirations of the Cancer Moonshot. In the past 5 years, the FDA issued an unprecedented 161 new approvals of therapeutic agents for various indications in adult patients with solid tumours. However, less than a third (27%) of the newly approved medicines are supported by unequivocal evidence of an overall survival benefit; most are supported by positive signals from surrogate end points. Herein, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 was used to evaluate the clinical value of the therapies granted FDA approval during the period 2017–2021. The results of this appraisal indicate a low level of clinical benefit for a substantial proportion (~20%) of the new indications, with most (~44%) providing intermediate benefit. The data suggest that, beyond increases in the sheer quantity of approvals, considerable improvement in the quality of the approved treatments is required to more confidently ensure that the clinical benefits are real and substantial enough to clearly justify the risks to patients.

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Fig. 1: Overview of FDA approvals granted in 2017–2021 of therapies for use in adults with solid tumours.
Fig. 2: Trends in the FDA-approval pathways and disease settings of treatments indicated for use in adults with solid tumours based on approvals granted during the period 2017–2021.
Fig. 3: Immuno-oncology agents approved by the FDA in 2017–2021 for the treatment of solid tumours in adults.
Fig. 4: ESMO-MCBS v1.1 grade distribution of immuno-oncology agents approved by the FDA in 2017–2021 for the treatment of solid tumours in adults.
Fig. 5: Trends in the primary end points supporting FDA approvals granted during the period 2017–2021 of therapeutic agents for use in adults with solid tumours.
Fig. 6: Temporal trends in the ESMO-MCBS v1.1 grade distribution of FDA approvals granted during the period 2017–2021 of agents for the treatment of advanced-stage solid tumours in adults.

References

  1. Cancer Moonshot Task Force. Cancer Moonshot: Report of the Cancer Moonshot Task Force (The White House, 2016).

  2. Cherny, N. I. et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann. Oncol. 26, 1547–1573 (2015).

    Article  CAS  PubMed  Google Scholar 

  3. Cherny, N. I. et al. ESMO-Magnitude of Clinical Benefit Scale version 1.1. Ann. Oncol. 28, 2340–2366 (2017).

    Article  CAS  PubMed  Google Scholar 

  4. Cherny, N. I. et al. Comparative assessment of clinical benefit using the ESMO-Magnitude of Clinical Benefit Scale version 1.1 and the ASCO Value Framework Net Health Benefit Score. J. Clin. Oncol. 37, 336–349 (2018).

    Article  PubMed  Google Scholar 

  5. Dafni, U. et al. Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules. ESMO Open 2, e000216 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fojo, T., Mailankody, S. & Lo, A. Unintended consequences of expensive cancer therapeutics–the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity: the John Conley Lecture. JAMA Otolaryngol. Head. Neck Surg. 140, 1225–1236 (2014).

    Article  PubMed  Google Scholar 

  7. US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. fda.gov, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication (2017).

  8. Ravaud, A. et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N. Engl. J. Med. 375, 2246–2254 (2016).

    Article  CAS  PubMed  Google Scholar 

  9. Mamtani, R. et al. Association between age and sex and mortality after adjuvant therapy for renal cancer. Cancer 125, 1637–1644 (2019).

    Article  CAS  PubMed  Google Scholar 

  10. Haas, N. B. et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet 387, 2008–2016 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Moore, K. et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 379, 2495–2505 (2018).

    Article  CAS  PubMed  Google Scholar 

  12. González-Martín, A. et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 381, 2391–2402 (2019).

    Article  PubMed  Google Scholar 

  13. Ray-Coquard, I. et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N. Engl. J. Med. 381, 2416–2428 (2019).

    Article  CAS  PubMed  Google Scholar 

  14. Gray, J. E. et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage III NSCLC–update from PACIFIC. J. Thorac. Oncol. 15, 288–293 (2020).

    Article  CAS  PubMed  Google Scholar 

  15. Hui, R. et al. Patient-reported outcomes with durvalumab after chemoradiotherapy in stage III, unresectable non-small-cell lung cancer (PACIFIC): a randomised, controlled, phase 3 study. Lancet Oncol. 20, 1670–1680 (2019).

    Article  CAS  PubMed  Google Scholar 

  16. Antonia, S. J. et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N. Engl. J. Med. 379, 2342–2350 (2018).

    Article  CAS  PubMed  Google Scholar 

  17. Antonia, S. J. et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N. Engl. J. Med. 377, 1919–1929 (2017).

    Article  CAS  PubMed  Google Scholar 

  18. Wolchok, J. D. et al. Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J. Clin. Oncol. 40, 127–137 (2022).

    Article  CAS  PubMed  Google Scholar 

  19. Reck, M. et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non–small-cell lung cancer with PD-L1 tumor proportion score ≥50%. J. Clin. Oncol. 39, 2339–2349 (2021).

    Article  CAS  PubMed  Google Scholar 

  20. Cortes, J. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 396, 1817–1828 (2020).

    Article  PubMed  Google Scholar 

  21. Cortés, J. et al. KEYNOTE-355: Final results from a randomized, double-blind phase III study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC [abstract LBA16]. Ann. Oncol. 32 (Suppl. 5), 1289–1290 (2021).

    Article  Google Scholar 

  22. Gyawali, B. et al. Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring. ESMO Open 6, 100117 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chi, K. N. et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 19, 194–206 (2018).

    Article  CAS  PubMed  Google Scholar 

  24. Fizazi, K. et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N. Engl. J. Med. 377, 352–360 (2017).

    Article  CAS  PubMed  Google Scholar 

  25. Fizazi, K. et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 20, 686–700 (2019).

    Article  CAS  PubMed  Google Scholar 

  26. Armstrong, A. J. et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J. Clin. Oncol. 37, 2974–2986 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Motzer, R. J. et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 20, 1370–1385 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Powles, T. et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 21, 1563–1573 (2020).

    Article  CAS  PubMed  Google Scholar 

  29. Choueiri, T. K. et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 384, 829–841 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Motzer, R. et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N. Engl. J. Med. 384, 1289–1300 (2021).

    Article  CAS  PubMed  Google Scholar 

  31. Tripathy, D. et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 19, 904–915 (2018).

    Article  CAS  PubMed  Google Scholar 

  32. US Food and Drug Administration. Guidance for Industry: Expedited Programs for Serious Conditions — Drugs and Biologics (U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), 2014).

  33. Beaver, J. A., Kluetz, P. G. & Pazdur, R. Metastasis-free survival–a new end point in prostate cancer trials. N. Engl. J. Med. 378, 2458–2460 (2018).

    Article  PubMed  Google Scholar 

  34. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH E9 statistical principles for clinical trials. ema.europa.eu, https://www.ema.europa.eu/en/ich-e9-statistical-principles-clinical-trials (1998).

  35. Powles, T. et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 21, 1574–1588 (2020).

    Article  CAS  PubMed  Google Scholar 

  36. Yau, T. et al. CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC) [abstract LBA38_PR]. Ann. Oncol. 30 (Suppl. 5), v874–v875 (2019).

    Article  Google Scholar 

  37. Spigel, D. et al. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆. Ann. Oncol. 32, 631–641 (2021).

    Article  CAS  PubMed  Google Scholar 

  38. Rudin, C. M. et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J. Clin. Oncol. 38, 2369–2379 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bardia, A. et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N. Engl. J. Med. 380, 741–751 (2019).

    Article  CAS  PubMed  Google Scholar 

  40. Garassino, M. C. et al. Health-related quality of life (HRQoL) in the KEYNOTE-189 study of pembrolizumab (pembro) or placebo (pbo) + pemetrexed (pem) + platinum (plt) for metastatic NSCLC [abstract]. J. Clin. Oncol. 36 (Suppl. 15), 9021 (2018).

    Article  Google Scholar 

  41. Powles, T. et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N. Engl. J. Med. 384, 1125–1135 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Powles, T. et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N. Engl. J. Med. 383, 1218–1230 (2020).

    Article  CAS  PubMed  Google Scholar 

  43. Colombo, N. et al. Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775) [abstract 726MO]. Ann. Oncol. 32 (Suppl. 5), S729–S730 (2021).

    Article  Google Scholar 

  44. Camidge, D. R. et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N. Engl. J. Med. 379, 2027–2039 (2018).

    Article  CAS  PubMed  Google Scholar 

  45. Colombo, N. et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N. Engl. J. Med. 385, 1856–1867 (2021).

    Article  CAS  PubMed  Google Scholar 

  46. Vuky, J. et al. Long-term outcomes in KEYNOTE-052: Phase II study investigating first-line pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer. J. Clin. Oncol. 38, 2658–2666 (2020).

    Article  CAS  PubMed  Google Scholar 

  47. Schmid, P. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21, 44–59 (2020).

    Article  CAS  PubMed  Google Scholar 

  48. Schmid, P. et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379, 2108–2121 (2018).

    Article  CAS  PubMed  Google Scholar 

  49. Golan, T. et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N. Engl. J. Med. 381, 317–327 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Golan, T. et al. Overall survival from the phase 3 POLO trial: Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. J. Clin. Oncol. 39 (Suppl. 3), 378 (2021).

    Article  Google Scholar 

  51. Gyawali, B., Hey, S. P. & Kesselheim, A. S. Evaluating the evidence behind the surrogate measures included in the FDA’s table of surrogate endpoints as supporting approval of cancer drugs. EClinicalMedicine https://doi.org/10.1016/j.eclinm.2020.100332 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Fundytus, A. et al. Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey. Lancet Oncol. 22, 1367–1377 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kantarjian, H. & Patel, Y. High cancer drug prices 4 years later–progress and prospects. Cancer 123, 1292–1297 (2017).

    Article  PubMed  Google Scholar 

  54. Howard, D. H., Bach, P. B., Berndt, E. R. & Conti, R. M. Pricing in the market for anticancer drugs. J. Economic Perspect. 29, 139–162 (2015).

    Article  Google Scholar 

  55. Vokinger, K. N. et al. Prices and clinical value of cancer drugs in the US and Europe–a cost-benefit analysis. Lancet Oncol. 21, 664–670 (2020).

    Article  CAS  PubMed  Google Scholar 

  56. Saluja, R. et al. Examining trends in cost and clinical benefit of novel anticancer drugs over time. J. Oncol. Pract. 14, e280–e294 (2018).

    Article  PubMed  Google Scholar 

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Acknowledgements

I thank the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) administrative coordinators N. Latino and M. Galotti for general support and for drafting the figures, and B. Gyawali, E. de Vries, H. Dressler, H. Goldwasser and A. Gabizon for providing feedback on early drafts of this manuscript. I am also grateful for general support from the Shaare Zedek Medical Center, ESMO, and my tolerant and supportive family. I am solely responsible for any errors in the information presented herein.

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  1. Department of Medical Oncology, Shaare Zedek Medical Center, Jerusalem, Israel

    Nathan I. Cherny

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Correspondence to Nathan I. Cherny.

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N.I.C. is Chair of ESMO-MCBS working group. The author declares no financial competing interests.

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Nature Reviews Clinical Oncology thanks C. Booth, C. A. Uyl-de Groot and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Cherny, N.I. An appraisal of FDA approvals for adult solid tumours in 2017–2021: has the eagle landed?. Nat Rev Clin Oncol 19, 486–492 (2022). https://doi.org/10.1038/s41571-022-00636-y

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