Treatment Process in Non-Small Cell Lung Cancer
Stephen Liu, MD:The choice of durvalumab after chemoradiation is entirely appropriate and reflects our current best practices. From the PACIFIC trial, we know that the addition of durvalumab versus placebo after completing definitive chemoradiation improved progression-free survival and improved overall survival. This is absolutely the right choice.
While there are some data for other checkpoint inhibitors, such as pembrolizumab in that setting, the randomized phase III data are with durvalumab and currently would be considered the standard of care and the appropriate agent to use in this setting.
I would typically want to start durvalumab within a month of completing radiation therapy. In the original PACIFIC trial, the original design mandated the start of durvalumab within 14 days of completing chemoradiation, and that proved to be somewhat clinically challenging. Patients are often quite ill and need a bit more time to recover. Because of some barriers to enrollment, that window was increased to 42 days. Currently, 14 to 42 days would be following the PACIFIC guidelines. There were some interesting subset data that suggested patients who received durvalumab a bit earlier seemed to have better outcomes. It’s not clear whether this reflects better performance status at that time, or lower burden of disease, or other confounders that might be built into that. Earlier initiation could build on potential synergy between radiation and checkpoint inhibitors, which could lead to better efficacy.
In theory, that could also lead to more toxicity, higher rates of pneumonitis. We’re just not sure yet, and I think it has to be individualized to the specific patient. Typically, I would start around 3 to 4 weeks after completing radiation. Though if patients had quite a bit of toxicity from chemoradiation, I would want them to be relatively well before initiating durvalumab, so I might have to wait a bit longer. If patients have very minimal toxicity, based on the radiation field and underlying lung function, then I might start a bit earlier. Technically, I’m aiming for about a month to start durvalumab, and then I would continue for 26 doses, which without delays would be about 1 year of therapy.
Ensuring patient fitness after CRT [chemoradiation therapy] is an ongoing challenge. It requires the support of your multidisciplinary team. Chemoradiation therapy is potentially curative treatment, but this can be quite toxic. I think as a thoracic oncologist, it’s probably the most toxic treatment that I would have to deliver. While we will see patients fairly frequently to judge their fitness for each dose of chemotherapy, the support along the way is of vital importance.
Early in the course of therapy, I am sure to introduce patients to our nutritionist, our dietitian, to be sure we’re meeting the caloric intake goals and needs. Really, those support systems for nutrition support are essential in minimizing the toxicity and maximizing the recovery from radiation therapy. Hydration is important, avoiding complications from hypovolemia, nephrotoxicity. I will often incorporate supplemental IV [intravenous] fluids toward the end of treatment. When I’m scheduling chemotherapy to coincide with their definitive radiation therapy, toward the second half of treatment also scheduling IV fluids 2, sometimes 3, times a week for the second half of radiation and beyond, knowing that I can cancel those if patients aren’t needing them and ensuring we’re hitting our nutrition goals to try to minimize that toxicity.
Pain medications, analgesics, are important to minimize pain. If we can minimize pain, we can maximize oral intake of food. While we’re dosing chemotherapycarboplatin and paclitaxel, we have to be sure that we don’t push the patients too far. We will push patients. Chemotherapy does play a role, but it’s important to realize radiation, I think, is the more important piece of treatment. Holding a dose of chemotherapy for patients who are particularly sick or having a lot of radiation toxicity may avoid delays in radiation, and that ultimately improve outcomes.
Judging the fitness of each patient before each dose of chemotherapy is critical to be sure we don’t push patients too far.
Assessing our patients before each dose of chemotherapy is important. Giving 1 dose too much of chemotherapy could really push patients too far, hamper their recovery, and be more detrimental in the long run.
Transcript edited for clarity.
Case: A 62-Year-Old Male With Stage III NSCLC
Initial presentation
- A 62-year-old man presented with a 2-month history of cough, wheezing, and loss of appetite
- PMH: Hypertension, medically treated
- SH: 30 pack-year smoking history; daughter to be married in 11 months, and wants to attend the wedding
- PE: Right lower lobe wheezing on auscultation
Clinical workup
- Labs: WNL
- PFT: FEV1/FVC 60%; DLCO 55%
- Chest/abdomen/pelvic CT showed a 6.1-cm solid pulmonary lesion in the right lower lobe, right hilar and intrapulmonary lymph node involvement; no evidence of distant metastases
- PET scan showed large focal hypermetabolic activity in the right lower lobe and small hypermetabolic activity in the surrounding area
- Contrast‐enhanced MRI of the head showed no brain metastases
- Bronchoscopic biopsy of the RLL mass and hilar node revealed squamous NSCLC
- Staging: T3N1M0 IIIA; ECOG PS 1
- Unresectable NSCLC based on the extent and location of disease
Treatment
- Patient was started on cisplatin 50 mg/m2on days 1,8,29 and 36; etoposide 50 mg/m2days 1-5 and 29-33; concurrent RT
- No disease progression after chemoradiation
- Durvalumab 10mg/kg IV q2W was started and dose was tolerated well
- Initial follow-up at 2 months showed partial response, with shrinkage of primary and nodal lesions
