Highs and lows in non-small cell lung cancer


5-year durvalumab data reads out amid record lows in new cancer diagnoses

Lung cancer continues to have a poor prognosis, which is largely attributed to diagnosis at an advanced stage.1,2   It seems that this situation has not been helped by the impact of the COVID-19 pandemic on screening and diagnosis.3

On the positive side, first-line treatment options for metastatic non-squamous non-small cell lung cancer (NSCLC) have expanded over the past couple of decades, providing more treatment options, including at later stages of the disease.4 Treatments have evolved from the reliance on platinum-doublet chemotherapy to the use of combination therapy with monoclonal antibodies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1).4

The 5-year data for durvalumab has recently read out from the PACIFIC trial,5-7 confirming OS and progression free survival (PFS) benefits when using this PD-L1 monoclonal antibody as a sequential therapy in patients with locally advanced, unresectable NSCLC following platinum-based, concurrent chemoradiation therapy.5-7

Speaking to the limbic, medical oncologist Professor Nick Pavlakis from the Royal North Shore Hospital discussed how the disruptions of the pandemic have affected lung cancer diagnosis and patient care. He also offered his perspectives on how the PACIFIC trial data reinforces the role of durvalumab as standard of care in advanced non-resectable NSCLC.

The far-reaching effects of the COVID-19 pandemic

The COVID-19 pandemic has affected many areas of life, including diagnosis and treatment of non-COVID-19 related illness.2   For lung cancer, referral data between March and April 2020 indicated a 50% decrease in GP referrals, with almost half (47%) of lung cancer and respiratory specialists reporting delays in suitably timed referrals for diagnostic procedures.8 Accordingly, Cancer Australia found that lung cancer-related diagnostic services in Australia were 9% lower than expected in 2020, equating to 3,884 fewer services, based on an analysis of Medicare Benefits Scheme (MBS) data.9

Experts are warning the full impact of later diagnoses is unlikely to become evident until a decade from now.10 Prof. Pavlakis explained that the pandemic has hit this area of medicine particularly hard. “For patients, the pandemic limited access to care, primarily due to lockdowns. For those with newly presenting symptoms who didn’t require a trip to the hospital, that may mean some missed diagnoses along the way. For those already in the system for treatment, increased healthcare system workloads and the modification in access due to the risks of spreading COVID-19 may have also affected the speed and/or type of care received. 5

Patient screening during the pandemic also saw disruptions, especially in aerosol generating procedures such as bronchoscopy as well as other screening services.2,16  Lung cancer surgeries, patients needing systemic treatments, ICU admission and mechanical ventilation were also often deprioritised, delayed or cancelled.10   While health care systems are trying to return to pre-pandemic levels of operation, it is estimated that there will be a 4.8–5.3 % increase in lung cancer deaths 5 years after diagnosis because of the pandemic.12 

The early prevention and avoidance strategy [for COVID-19] was a good initiative. When more relaxed measures occurred, more and more clinicians and support staff had to isolate, resulting in reduced patient care. Despite the availability of telehealth, patients still had restricted access to clinics for treatment and follow up checks,” said Prof Pavlakis.

The PACIFIC trial: OS and PFS data for durvalumab

The PACIFIC trial primary endpoints were OS and progression-free survival (PFS). Significant improvements were seen in OS and PFS in the  durvalumab group, with an OS of 66.3% (95% confidence interval [CI], 61.7 to 70.4) vs 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided p=0.005). The medium PFS for the durvalumab group was 17.2 months (95% CI, 13.1 to 23.9) vs 5.6 months (95% CI, 4.6 to 7.7) in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). Durvalumab significantly prolonged OS, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; p=0.0025).  Regarding safety, maximum-grade 3 or 4 adverse events of any cause occurred in  30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group.17

PACIFIC 5-year data further supports durvalumab as ‘standard of care’

Updated data was presented following the last patient completing study treatment in May 2017. As of early 2021, median OS was 47.5 for durvalumab vs 29.1 months in the placebo group (stratified HR 0.72, 95% CI 0.59–0.89), with the 60-month OS rates being 42.9% and 33.4% with durvalumab vs placebo, respectively. Median PFS was 16.9 for durvalumab vs 5.6 months in the placebo group (stratified HR 0.55, 95% CI 0.45–0.68); 60-month PFS rates were 33.1% and 19.0%, respectively.5 

The release of this data is a reminder of treatment options available to those diagnosed with advanced NSCLC, highlighting the importance of timely referral, detection and diagnosis. After nearly two decades of efforts to improve the prognosis of advanced NSCLC, for those patients with unresectable but potentially curable NCSLC, durvalumab fills an unmet need.18,19

The PACIFIC trial OS data stands out as strong evidence for those patients with stage III non-resectable NSCLC. This trial unequivocally offers a new standard of care for patients, as agreed in the medical community,” said Prof. Pavlakis.

Disclosure 

This article was sponsored by Astra Zeneca. Any views expressed in the article are those of the expert alone and do not necessarily reflect the views of the sponsor. Before prescribing, please review the Imfinzi product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.

References

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  6. US National Library of Medicine. A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC) [Internet]. Clinical Trials.gov; 2019 Jan. 30 [updated 2022 Jan. 24; cited 2022 Feb 9]. Available from: https://clinicaltrials.gov/ct2/show/NCT02125461. [About 2 screens]
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  8. IQVIA MEDIBUS 2020
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  14. NSW Government. In focus Symptom Profile [Internet]. NSW Health. 2020 Dec. 12. [Updated 2020 Dec; cited 2022 Feb 9]. Available from: https://www.health.nsw.gov.au/Infectious/covid-19/Documents/in-focus/symptom-profile-20200701-20201212.PDF
  15. NSW Government. Testing positive to COVID-19 and managing COVID-19 safely at home [Internet]. NSW Health. 2020 Feb. 06 [Updated 2020 Feb. 06; cited 2022 Feb. 9]. Available from: https://www.nsw.gov.au/covid-19/management/advice-for-confirmed
  16. Van Haren R, et al. J Am Coll Surg. 2021;232(4):600–05.
  17. Antonia SJ, et al. N Engl J Med. 2018; 379(24);2342–50.
  18. Cheema PK, et al. Curr Oncol. 2019;26(1):37–42.
  19. McCall NS, et al. Clin Cancer Res. 2018;24(6):1271–76.

 

 

 

 

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