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ASTRO 2019: Patterns of Disease Progression in Patients With Unresectable Stage III NSCLC: Analysis of the PACIFIC Trial


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Andreas Rimner, MD, of Memorial Sloan Kettering Cancer Center, presented an update of the landmark PACIFIC trial at the 61st Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA-6).

In earlier reports from the randomized phase III trial, Antonia et al had evaluated the addition of the anti–programmed cell death ligand (PD-L1) antibody durvalumab in patients with stage III unresectable non–small cell lung cancer (NSCLC) with no disease progression following two or more cycles of platinum-based chemoradiation. Results of the study showed a significant improvement in progression-free survival, the primary endpoint. Later follow-up revealed a significant improvement in overall survival, the second primary endpoint.

As a result of these findings, adjuvant durvalumab became the new standard of care for patients with stage III unresectable NSCLC whose disease had not progressed after two or more cycles of platinum-based chemoradiotherapy.


“With this type of cancer, you can achieve some control of the tumor within the lung, but it almost invariably comes back elsewhere in the body and there are limited options for what we can do. To have a treatment that truly reduces the rate of lesions developing distantly, and reduces the frequency of these distant lesions, is a major step forward and really improves the outlook for these patients.”
— Andreas Rimner, MD

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Patterns of Disease Progression

In this new analysis, Dr. Rimner and an independent team of researchers from the United States, the Netherlands, and the United Kingdom reanalyzed computed tomography (CT) scans from the PACIFIC study, and found that fewer than half of patients (45.4%) in the durvalumab-treated arm experienced disease progression or died, compared to two-thirds of patients (64.6%) in the placebo arm. For most patients in both arms, new cancer lesions first appeared locally within the thorax. Of those treated with durvalumab, 36.6% had first new cancer growth only within the thorax compared to 48.1% of those not treated with durvalumab; 6.9% of patients in the durvalumab-treated group had first new cancer growth only outside the thoracic area vs 13.1% in the placebo arm.

Of those in the durvalumab-treated arm, 1.9% experienced first cancer growth both inside and outside the thoracic area vs 3.4% of those in the placebo arm, with 8.8% of those patients experiencing new lesions outside the thoracic area first vs 16.5% in the placebo arm. 

Time to Distant Metastasis

For most patients who experienced new, distant metastases as the first failure site, those lesions occurred in the brain in 61.9% of durvalumab-treated patients and 66.7% of patients who received placebo with new lesions outside the thoracic area. The time it took for new lesions to grow was also longer in each region for patients in the durvalumab-treated arm compared to those in the placebo arm.

This was also true for patients who only experienced local tumor growth (25.2 months vs. 9.2 months; hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.43–0.70), as well as for patients who only experienced distant tumor growth (median not reached in either group; HR = 0.41, 95% CI = 0.27–0.63) and for patients who experienced tumors in both areas (median not reached in either group; HR = 0.48, 95% CI = 0.28–0.82).

“It’s notable how the addition of durvalumab significantly decreased the distant progression of disease,” said Dr. Rimner. “With this type of cancer, you can achieve some control of the tumor within the lung, but it almost invariably comes back elsewhere in the body and there are limited options for what we can do. To have a treatment that truly reduces the rate of lesions developing distantly, and reduces the frequency of these distant lesions, is a major step forward and really improves the outlook for these patients.”

Progression Remains a Challenge

Lung cancer is the leading cause of cancer death worldwide. Most patients with NSCLC, which accounts for 85% of all lung cancers, experience some continued cancer growth after chemoradiation—approximately half within 2 years, and 70% to 80% after more than 2 years, explained Dr. Rimner. 

“When cancer returns in just one or two areas, it can be amenable to aggressive local therapies. There is increasing evidence that local ablative therapies may further extend survival for these patients. We can’t say that this is definitively what should be done, as this trial didn’t address that question. But it’s being evaluated in several phase II studies and currently being investigated in ongoing phase III studies, including NRG-LU002.”

This new analysis of disease progression data adds support to the decision to make the addition of durvalumab to chemoradiation a standard practice for some patients with NSCLC, Dr. Rimner indicated.

 

Disclosure: For full disclosures of the study authors, visit astro.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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