During a Targeted Oncology™ Case-Based Roundtable™ event, Edward S. Kim, MD, MBA, and participants discussed the PACIFIC and PACIFIC-R studies of durvalumab in patients with unresectable stage III non–small cell lung cancer.
Edward S. Kim, MD, MBA (Moderator)
Physician-in-Chief, City of Hope Orange County
Vice Physician-in-Chief, City of Hope National Medical Center
Professor, Department of Medical Oncology & Therapeutics Research
Construction Industries Alliance City of Hope Orange County Physician-in-Chief Chair
Newport Beach, CA
DISCUSSION QUESTIONS
- Were you familiar with the PACIFIC-R observational study (NCT03798535) and/or its results?
- What is your reaction to those data? Which data ismost impactful and relevant to your practice?
- How do they compare to your own experiences with use of durvalumab (Imfinzi) afterchemoradiotherapy?
- Would you use consolidation durvalumab in patients with PD-L1 levels less than 1%?
- What about patients with a knownEGFRmutation?
- How do you manage adverse events (AEs) to allowpatients to receiveoptimal therapy of 12 months?
EDWARD S. KIM, MD, MBA: Were you familiar with the PACIFIC-R study and/or its results? How did they compare with your experience? Would you use consolidation durvalumab in those patients with less than 1% PD-L1? What if this was stage IIIC disease? And how do you all manage those AEs?
RUPESH PARIKH, MD: Considering there are few options for maintenance [therapy], I would still tend to use durvalumab [Imfinzi] even if the PD-L1 level was less than 1%, because they usually don’t tolerate maintenance chemotherapy that well after 4 to 6 cycles unless you want to put them on pemetrexed [Alimta] maintenance.
HARRY MENON, DO: I've seen these data before and I agree. I would use durvalumab in these cases even despite that because from a maintenance standpoint, you don’t have better options here and I'm going to try and do as much as possible.
KIM: Does anyone have challenges with AEs and management? Are you going for 12 months, or do you think once you hit 6 months or 8 months you're in the clear?
PARIKH: I try and go 12 months. The challenge I have is at 12 months is whether to continue it if I still see evidence of disease that is ‘lukewarm’ on the PET scan.
THAI HO, MD: I tend to stop at 12 months because I think you're not going to deepen the responses with more immunotherapy past a year.
MENON: I would just go for the 12 months and then monitor.
DARSHIL SHAH, MD, MPH: Twelve months is the goal, but I usually do run into some kind of autoimmune toxicity before 12 months and [so I] manage [and] sometimes use prednisone, but 12 months is the goal. Once I reach that I usually stop.
KATHERINE THOMAS, MD: I don’t have anything to add. I only have ever done 12 months. I haven't gone any [longer].
KIM: I think 12 months is the goal, and I wouldn’t go past 12 months. We’re all tempted by that especially when the patient looks good. It is the same thing in the metastatic setting when we’re giving maintenance. What do you do when you stop? It's hard to say, but the study used 12 months so I would just use 12 months and then let patients go at that point and follow them with scans. Short of some of immune-related AEs like interstitial lung disease and others, [which] we know how to manage through, we want to keep going. It doesn’t surprise me that the real-world data shows it's a little bit better because I think [physicians] are more comfortable.
ROBERT YOO, DO: Did we talk about [if] a patient had the EGFR mutation?
KIM: No, we have not yet.
YOO: I’ve had 2 cases. I know the phase III LAURA study [NCT03521154] is not yet published but I'm doing…maintenance osimertinib [Tagrisso]. I looked at the subset analysis on EGFR; I think it was 9 or 10 patients from PACIFIC.1 There was no benefit from durvalumab, so I was just doing maintenance osimertinib after chemoradiation.
KIM: [This is] definitely extrapolation of the data. Biomarker testing [was not] required in PACIFIC so just as you pointed out, the data are [limited] in there. We get a little worried to give IO [immunotherapy] in the metastatic setting if we have [a patient with] an EGFR mutation [in their disease]. If you're testing, and you want to avoid giving IO in your locally advanced patients who have EGFR mutations, this study didn’t answer that question. But I think extrapolating some of those data from the other experiences across lung cancer [treatment] is rational at this point.
YOO: In your practice [would you] offer maintenance osimertinib instead of durvalumab if you have EGFR-mutated [lung cancer]?
KIM: In unresectable disease it's not necessarily a standard practice. It's very much debated, and you wonder if you just [should] wait until progression [if] there’s an EGFR mutation or if there's actual benefit in the unresectable [population] right now. That [approach] is not a standard. I didn’t say it was wrong. I just said it wasn’t standard, so let me just be clear about that.
BRIAN VICUNA, MD: In the PACIFIC-R data, most of those patients started durvalumab more than 6 weeks after the chemoradiation and their progression-free survival was 5 months better.2 Do you think that was correlated to waiting longer after chemoradiation, or a separate reason?
KIM: I don’t know if it was necessarily correlated with that. Even [with] the earlier start of the durvalumab, it’s an unsupervised analysis. It's harder sometimes in other countries to get in to start treatment after diagnosis and then to get to the next treatment. We see that in [the United Kingdom] and some European countries, etc. I don’t know if I’d necessarily say it's a correlation right now. These were just observational data.
Remember there was also sequential chemotherapy/radiotherapy that was done which we know is not as superior per se, as concurrent [chemoradiation] but those patients had some different situations physiologically. I would take it as real-world evidence that durvalumab works but those details that we talk about as far as when to start, when the optimal time to start is, duration, etc; those are still going to linger. I would just go with the protocol that was in the randomized study. We will be debating those aspects and the merits of real-world observational data vs the randomized study data.
SHAH: [I have] a theoretical question. I know in the PACIFIC study they didn’t look at the biomarkers, but if you find someone who has STK11/KEAP1 mutation and you know that IO monotherapy is not going to be that effective, would that make an impact on the decision as far as using durvalumab?
KIM: I wouldn’t use that as my guidance in stage III [disease], even in the metastatic setting. Although there are increasing data with several of these markers, it wasn’t something that stops us right now if that’s the best option, because we’re not necessarily seeing AEs as you would with the EGFR mutations of that trial. It might be less effective, but it doesn’t say it's harming the patient from that standpoint. In the stage III setting, if you happen to have those [biomarkers] in front of you, you can certainly discuss it with the patient. But there were no data out of PACIFIC that looked at those, so it's hard to say if you should use those to guide therapy, especially a therapy that has shown such benefit.
References:
1. Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer.J Clin Oncol. 2022;40(12):1301-1311. doi:10.1200/JCO.21.01308
2. Girard N, Bar J, Garrido P, et al. Treatment characteristics and real-world progression-free survival in patients with unresectable stage III NSCLC who received durvalumab after chemoradiotherapy: findings from the PACIFIC-R study.J Thorac Oncol. 2023;18(2):181-193. doi:10.1016/j.jtho.2022.10.003
FAQs
Is durvalumab approved for Stage III lung cancer? ›
November 20, 2020 - The FDA has approved durvalumab for an additional dosing option, a fixed dose of 1500 mg every 4 weeks, in the approved indications of unresectable stage III non-small cell lung cancer after chemoradiation and previously treated advanced bladder cancer.
What is the success of durvalumab? ›An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.
How is Stage 3 unresectable lung cancer treated? ›Chemotherapy and Radiation
8 You may receive 2-4 cycles of chemotherapy with radiation, then immunotherapy. The treatment for stage 3 NSCLC doesn't always cure cancer, but it can be curative. And even when it isn't a cure, treatment can allow you to enjoy a longer life.
The standard of care for patients with stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT) followed by 1 year of adjuvant durvalumab. Despite the survival benefit granted by immunotherapy in this setting, only 1/3 of patients are alive and disease free at 5 years.
What is the best treatment for Stage 3 lung cancer? ›In most cases, doctors will treat stage 3 lung cancer with a combination of treatments: Chemotherapy: This is often effective in treating lung cancer. Radiation therapy: This may be useful in shrinking a tumor before a person has surgery. Surgery: This can help in situations where cancer is not yet widespread.
What is the new lung cancer treatment for 2023? ›Osimertinib (also known as Tagrisso), a new drug from AstraZeneca, could reduce the risk of patients with early-stage non-small cell lung cancer (NSCLC) dying by 51%. That's according to results from the Phase 3 ADAURA trial, which looked at 682 patients with early-stage NSCLC.
How long can you be on durvalumab? ›You usually have durvalumab every 2 weeks. It takes about an hour each time you have it. You have durvalumab for as long as it works and the side effects are not too bad. You usually have it for up to a year.
Which is better Keytruda or Imfinzi? ›Imfinzi and Keytruda work in a similar way to treat several forms of cancer. However, they're different in some of their side effects. And Keytruda is used to treat more types of cancer than Imfinzi. If you have questions about which drug may be better for your treatment plan, talk with your doctor.
What are the toxicities of durvalumab? ›Regarding the types of pulmonary toxicity, besides interstitial lung disease and radiation-induced pneumonitis, diverse signals were detected for lung-related AEs associated with durvalumab, including lung inflammation, lung damage, respiratory failure, bacterial pneumonia, and pneumothorax.
How long can Stage 3 lung cancer stay in remission? ›Stage 3. Almost 15 out of 100 people (almost 15%) with stage 3 lung cancer will survive their cancer for 5 years or more after they're diagnosed.
How long can you live with Stage 3 lung cancer with no treatment? ›
Stage 3 Lung Cancer Life Expectancy Without Treatment
Treatment can be physically, mentally, and fiscally taxing. Without treatment, untreated lung cancer patients live an average of 7 months. Lung Cancer Center understands the inability to undergo cancer treatment due to expenses.
But stage 3 cancer isn't a death sentence. Survival rates are improving, and researchers are continually discovering and testing new targeted drugs and immunotherapies.
How many people beat Stage 3 lung cancer? ›The five-year relative survival rate for localized cancer is 29 percent, and that rate drops to 18 percent when it spreads regionally (and 3 percent when it spreads to more distant areas of the body).
What are the chances of beating Stage 3 lung cancer? ›About 1 in 3 people diagnosed with stage IIIA lung cancer live for at least 5 years after their diagnosis. For stage IIIB, the average 5-year survival rate is 26%. For stage IIIC, it's 13%.
How effective is durvalumab for lung cancer? ›Farago said, is that 1 year after patients were randomly assigned to the different treatments, 54% of patients in the durvalumab group were still alive, versus only 40% of those in the control group. And at 18 months, 34% and 25% of patients remained alive in the durvalumab and control groups, respectively.
What is the first line treatment for Stage 3 lung cancer? ›For SCLC, chemotherapy is a standard first-line treatment. For NSCLC, first-line treatment may consist of chemotherapy, radiation and/or surgery.
What is the newest treatment for lung cancer? ›Immunotherapy Approvals
In 2022, one already approved drug received additional use for lung cancer patients. This drug is Libtayo (cemiplimab-rwlc) which is a PD-1 inhibitor.
The current 5-year survival rates for stage 3 breast cancer are 86% for females and 83% for males. However, many factors can influence a person's life expectancy after a breast cancer diagnosis. A doctor can provide more detailed, personalized information.
What is the great debates in lung cancer 2023? ›The 2023 Great Debates and Updates in Lung Cancers is a multi-day, debate-driven conference focusing on the treatment of thoracic oncology. A comprehensive overview of the most significant advances in the treatment of lung cancer, as well as valuable take-home information, will be discussed.
Is there any hope for advanced lung cancer? ›Metastatic lung cancer means that the cancer has spread from where it started in the lung. It is also called advanced lung cancer. Unfortunately advanced cancer can't usually be cured. But treatment might control it, help symptoms, and improve your quality of life for some time.
What is immunotherapy for Stage 3 lung cancer? ›
Immunotherapy is a type of lung cancer treatment that uses medicine to activate your own immune system to recognize and kill cancer cells.
Why stop immunotherapy after 2 years? ›What is your reasoning for stopping treatment with immunotherapy after 2 years? The [biggest one is] AEs; some patients start experiencing chronic AEs, such as fatigue or arthralgias. We also face the issue of costs and the sustainability of our healthcare system. These drugs are not cheap.
How much longer can you live with immunotherapy? ›In her study, 70% of the patients who were able to complete 2 years on the chemo-immunotherapy combination were still alive at five years. They get infusions every three weeks for those two years, but most can work during treatment. "The quality of life of these patients is quite high," Garassino said.
Can you stay on immunotherapy indefinitely? ›Studies show that among patients who do respond positively to immunotherapy, the beneficial response lasts longer than with chemotherapy. If it's working for you, treatment may continue on a long-term basis, allowing us to manage certain cancers like a chronic illness.
What is the most successful immunotherapy drug? ›Checkpoint inhibitors are a form of cancer immunotherapy — treatments that stimulate the immune response to cancer cells. Checkpoint inhibitors are not the first form of cancer immunotherapy, but they are, so far, among the most successful, particularly in melanoma.
Which cancers respond best to immunotherapy? ›Skin cancers are common, often diagnosed at an early stage, and among the first cancers to respond to immunotherapy.
What is the new indication for IMFINZI? ›Imfinzi Receives New FDA Indication for Advanced or Metastatic Biliary Tract Cancer. On September 2, 2022, the FDA accelerated the approval of durvalumab (Imfinzi; AstraZeneca), a PD-L1 inhibitor, in combination with gemcitabine and cisplatin, for adults with locally advanced or metastatic biliary tract cancer.
Does durvalumab shrink tumors? ›Durvalumab is an antibody (a type of human protein) that works by blocking a body substance called Programmed Death-Ligand 1 (PD-L1). Blocking PD-L1 helps the body's immune system attack cancer cells. Research has shown that durvalumab can slow tumor growth and shrink tumors in some people with cancer.
How much does durvalumab cost? ›| Variable | Baseline value | Range |
|---|---|---|
| Drug costs in the US, $/per cycle | ||
| Gemcitabine | 15.06 | 12.04 |
| Cisplatin | 8.72 | 6.97 |
| Durvalumab | 11,730 | 9,384 |
Durvalumab received its first global approval on 1 May 2017 in the USA for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy ...
At what stage is lung cancer most curable? ›
For patients who have small, early-stage lung cancer, the cure rate can be as high as 80% to 90%. Cure rates drop dramatically as the tumor becomes more advanced and involves lymph nodes or other parts of the body.
Can lung cancer go into remission with immunotherapy? ›It is being used in several cancer types, including advanced metastatic lung cancer. Overtime, immunotherapy worked to slow the progression of cancer. “Her cancer is now quiet and in remission.
Can NSCLC go into remission? ›About 80 percent of cases achieve remission. However, remission lasts less than a year in most cases. Few cases are cured.
What is the life expectancy of someone with incurable lung cancer? ›Five-year survival rates for people who have SCLC are: 27% if it hasn't spread outside your lung. 16% if it's spread to nearby areas. 3% if it's spread to distant parts of your body.
What is the life expectancy of someone on immunotherapy for lung cancer? ›Researchers investigated the 5-year outcome of an immunotherapy drug on early-stage lung cancer. 80% of those who took the immunotherapy drug survived after 5 years, whereas survival rates from standard treatments are 36–68%.
What is the success rate of radiation therapy for lung cancer? ›The overall five-year survival rate for all stages is 25%. By the three groupings, five-year survival is: Local: 63% Regional: 35%
What is the chemotherapy treatment for Stage 3 lung cancer? ›The chemotherapy drug combinations that may be used to treat non−small cell lung cancer are: cisplatin with vinorelbine or etoposide – most common 2 combinations. cisplatin (or carboplatin) and gemcitabine. cisplatin (or carboplatin) and docetaxel (Taxotere)
Is durvalumab approved for lung cancer? ›AstraZeneca's Imfinzi (durvalumab) in combination with Imjudo (tremelimumab) plus platinum-based chemotherapy has been approved in the US for the treatment of adult patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).
When is durvalumab approved for NSCLC? ›On November 10, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab (Imfinzi, AstraZeneca Pharmaceuticals) and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal ...