Chicago, Ill -- AstraZeneca‘s Imfinzi (Ingredient: durvalumab) has demonstrated superior overall survival (OS) compared to placebo when given to unresectable stage-3 non-small cell lung cancer (NSCLC) patients whose disease did not progress after platinum-based chemotherapy and radiation therapy.

The finding came from the latest three-year follow-up data of the company’s randomized, blinded PACIFIC phase 3 trial presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Ill., from June 1-5.

Korea Biomedical Review met with Dr. Giovanni Melillo, Vice President and Head of AstraZeneca Immuno-Oncology Global Medical Affairs, to see how the company views the result of the trial and what it has planned for in the future.

Question: What was the difference between the newly published data and the previous one? What were the positive signals, and what were the unexpected ones?

Answer: In 2018, two-year OS results from the PACIFIC trial demonstrated an unprecedented survival advantage, with a 32 percent reduction in the risk of death for NSCLC patients receiving Imfinzi who had not progressed from chemoradiation therapy (CRT) compared to patients who received CRT alone.

At ASCO 2019, we presented three-year OS results from PACIFIC showing that Imfinzi delivered a durable and sustained clinical benefit for patients over a more extended period, with 57 percent of patients alive at three years compared to 43.5 percent on placebo.

Since its first approval in 2017, Imfinzi has remained the only immune-oncology (IO) therapy approved in patients with unresectable stage III NSCLC who have not progressed following CRT. With this longer-term data, the PACIFIC trial has reaffirmed Imfinzi as the standard of care in this setting, where there had been limited advancements in systemic treatment for more than a decade.

Q: In addition to increasing progression-free survival (PFS), the three-year data showed that the overall survival is above 50 percent. Do you expect such numbers to continue? If so, how much?

A: We’re optimistic this survival trend will continue as we move toward the five-year landmark with Imfinzi in this curative-intent setting.

These findings for Imfinzi are another example of our focus on bringing long-term survival benefits to patients who still have a chance of being cured. It is our ambition to expand this possibility to as many patients as possible, pursuing a development strategy focused on understanding how more patients with unresectable stage III NSCLC may benefit from durvalumab, and bringing these long-term survival benefits to earlier stages and lines of therapy.

Q: The study only administered Imfinzi for a year after chemo and still had a 10 percent lead in OS compared to the placebo. However, given that the number of survivors has been steadily declining, do you wonder if the patients could have stayed on the treatment longer?

Also, is the company conducting additional studies that show the best effect of Imfinzi over the period of administration?

A: We are excited that Imfinzi delivered a durable and sustained clinical benefit for patients over a more extended time, with 57 percent of patients alive at three years compared to 43.5 percent on placebo.

Building on the evidence of sustained survival benefit in unresectable stage III NSCLC in PACIFIC, we have initiated several studies focused on how to further improve on the clinical benefit provided by the PACIFIC regimen. We have initiated several studies in patients with stage III unresectable NSCLC, including PACIFIC 2, where Imfinzi is given concurrently with CRT and for a longer duration (i.e., until progression of the disease).

Q: More patients in the placebo arm received subsequent therapy. Was this simply because many patients had their disease progress, or was there another reason?

A: The PACIFIC data show that patients who received Imfinzi had longer progression-free survival (PFS) and fewer progression events compared to placebo. Because of this, fewer patients on Imfinzi required subsequent treatment and those that did, needed it much later, as measured by time to first subsequent therapy or death. It is important to emphasize that patients on Imfinzi had a significant overall survival benefit compared to placebo, even though many patients on the placebo arm went on to receive immunotherapy once their disease progressed.

Q: As the prognosis of chemotherapy was poor and painful in the past, many patients opted not to receive the treatment. However, as the PACIFIC data showed high OS, can we view this as a reason for ensuring patients undergo chemoradiation therapy?

A: We’ve seen an unprecedented overall survival benefit in patients who have not progressed following CRT - providing a strong rationale for encouraging patients to undergo treatment with the PACIFIC regimen of chemoradiation therapy followed by Imfinzi.

Before the PACIFIC study, there was no available treatment for patients who did not progress after CRT, and the only option was “watch and wait.”

We are committed to improving on the results of the PACIFIC study, and we are exploring other settings where durvalumab may provide significant benefits for patients. We’ve initiated several trials in earlier settings of NSCLC to examine the potential for treating patients with Imfinzi before or after surgical resection of the primary tumor and are looking forward to seeing the results for Imfinzi in these earlier stages of the disease.

Q: Are there any other researches that the company is conducting or planning in this area?

A: AstraZeneca has several ongoing trials focused on testing Imfinzi in earlier stages of NSCLC (stages I-III) in potentially-curative settings. The phase 3 PACIFIC-2 trial design, presented at the ASCO annual meeting, is evaluating Imfinzi given concurrently with CRT in patients with unresectable, stage III NSCLC. In phase 2 PACIFIC-6 trial, Imfinzi is being tested in the same population following sequential chemotherapy and radiation therapy.

Additional trials assess Imfinzi in the neoadjuvant setting (before other treatments) in stage II and III NSCLC patients (AEGEAN) and the adjuvant setting (following the primary treatment) in stage I to III. The phase 3 PACIFIC-4 trial is testing Imfinzi in unresected stage I and II NSCLC patients following definitive stereotactic body radiation therapy (SBRT).

AstraZeneca is also testing novel combinations with Imfinzi in two phase 2 platform trials in both unresectable, stage III disease (COAST) and in resectable stage I-III disease starting before surgery (NeoCOAST), to help find solutions for NSCLC patients not benefiting from currently-available therapies.