CRT for Locally Advanced NSCLC

Hossein Borghaei, DO, MS:Before the PACIFIC data, we had limited options for patients who had unresectable non—small cell lung cancer. We made progress by figuring out that concurrent chemoradiation is better than sequential chemotherapy radiation. Unfortunately, not a lot of our patients can get concurrent chemoradiation because of the potential toxicities.

We looked at different doses of radiation—and byweI mean the oncology community, not me personally of course—the addition of different drugs to chemotherapy backbone, and using consolidative chemotherapy after the concurrent chemoradiation was completed. But none of those really had any meaningful impact on the survival of the patients.

And, in fact, unfortunately, some of them were associated with higher levels of toxicity. So before the PACIFIC data, we were limited to concurrent chemotherapy radiation, followed by a couple of doses of sort of what we call big doses or systemic doses of chemotherapy, depending on the regimen that was used. And the patient would have gone under a period of observation, which would have been a regularly scheduled CAT [CT; computed tomography] scan and office visit to see if there is evidence of recurrence. So there really wasn’t a whole lot more for us to offer to these patients after initial chemotherapy radiation.

The use of chemotherapy along with radiation, again, has been investigated. Over decades, we’ve had chemotherapy regimens such as the use of cisplatin and etoposide as 1 potential regimen, and the use of weekly carboplatin and paclitaxel as another regimen. There have been arguments for and against the use of a regimen such as cisplatin-etoposide, where you can use almost full doses of both drugs, thinking that full doses of chemotherapy drugs would give you better systemic control versus a lower dose of weekly carboplatin-paclitaxel. That is followed by systemic doses of both these agents, again to achieve higher levels of systemic control of the disease.

There have been a couple of head-to-head comparison studies, at least 1 in particular, where the choice of chemotherapy didn’t seem to matter much in terms of improving PFS [progression-free survival] or overall survival of patients who were getting concurrent chemotherapy radiation. Toxicity, however, was clearly different among different regimens used. The rates of esophagitis and other toxicities could be different based on the choice of chemotherapy that one uses.

In the case of a patient with adenocarcinoma, another regimen that was investigated was the use of cisplatin and pemetrexed. And again, that regimen was not shown to have superior overall survival, but the toxicity is a little bit different. So from the perspective of improving clinical efficacy endpoints, the choice of chemotherapy didn’t seem to matter as far as I’m concerned.

In a patient who has squamous cell carcinoma, the options are, again, the weekly carboplatin-paclitaxel, such as the one that this patient got, versus using cisplatin-etoposide. Obviously, the use of cisplatin in someone who’s a little bit older with a lower performance status, maybe with compromised renal function, would be a little bit more difficult. But with active care and follow-up, it is possible. So I would say most practitioners, and me included, would choose a chemotherapy backbone that we think our patient can tolerate in terms of toxicities.

To some level, it has to do with the clinician’s comfort level with the particular regimen, and to some extent, what a clinician thinks that a patient can tolerate in terms of the toxicities associated with particular regimens. All of these regimens appear to be equally effective when combined with radiation.

The majority of the patients who get concurrent chemoradiation would have some response. Radiation is very effective, and local control. Chemotherapy acts as a synthesizer to radiation and also as having a direct cytotoxic effect. So the majority of patients who receive chemotherapy and radiation have a response. The question is how durable the responses are. Obviously, there are adverse effects associated with both treatments such as development of esophagitis that makes it a little bit difficult for patients to swallow for a few weeks. Most of these are transient, but obviously a patient requires active support through these kinds of events.

From time to time, obviously, again, the use of chemotherapy and radiation can be associated with hematologic toxicities such as neutropenia and anemia. They’re manageable, but clearly, if somebody is neutropenic, administration of chemotherapy, especially if you’re using a weekly regimen, might not be possible or feasible. So there are clearly issues like that which one needs to pay attention to. If I use a weekly regimen, I see my patients every other week, basically. Sometimes they’re on a weekly basis, depending on adverse effects and how much concern I have for them in terms of tolerability. Obviously, they won’t be getting daily radiation, and they are being monitored and there are nurses and physicians who see their patients on a regular basis. So I think we can pick up these toxicities and try to manage them.

But from a response point of view, I think the majority would end up having a response. A lot of my patients do get fatigue, so they do require a little time to recover. And I think these are all issues that most oncologists and radiation oncologists who use these regimens are familiar with and monitor their patients for. It’s not the easiest regimen for physicians and patients to go through, but again, as I said, it tends to be highly effective, at least initially in terms of regaining control over cancer that’s growing aggressively.

For a patient who is neutropenic, obviously we hold chemotherapy. We don’t use growth-factor support during radiation because that’s obviously contraindicated. Very rarely at our center do we hold radiation, unless a patient is very, very sick, requiring hospitalization, and is febrile or has issues like that. Esophagitis is 1 of the major issues. Again, we try to manage that by going over pain management with the patients, using proton pump inhibitors or other means to control any potential reflux disease, and instructing the patient as to the kind of diet that they can have to get them over the period of esophagitis. It’s a little bit variable from patient to patient, and the severity also varies, again, depending on the kind of chemotherapy that one is using. But over the years, we have managed, in sort of a multidisciplinary team approach, the pain and the esophagitis and issues like that.

Occasionally, patients can develop pneumonitis. I have to say that I haven’t seen someone develop rapidly progressing pneumonitis during chemoradiation, but theoretically, something like that could happen. That obviously poses significant issues in terms of how to complete the regimen and the course of treatment. Hematologic toxicities other than neutropenia, if there is significant anemia, we usually manage with transfusions. Obviously, a patient who is febrile is hospitalized with the usual precautions that we use for a febrile patient.

For nausea and GI [gastrointestinal adverse] effects, again, we’re fortunate to live in a time in which we have really good antiemetics for the management of these patients. The one that’s most difficult for me to manage and to help my patients through is fatigue. And I think we try to encourage our patients to remain active as much as possible. But for some patients, the fatigue, I would say, affects their quality of life a little bit more than anticipated. And again, that is 1 of the more difficult adverse effects of this particular regimen for patients to tolerate.

Transcript edited for clarity.

Case: A 72-Year-Old Female With Stage IIIB NSCLC

Initial presentation

• A 72-year-old woman presented with a 17-lb weight loss and dyspnea
• PMH: HTN and hyperlipidemia
• PSH: Laparoscopic cholecystectomy
• SH: Smoked 3 packs/day for 30 years; Quit 5 years ago
• PE: Unremarkable

Clinical workup

• Imaging:
  • Chest x-ray showed a left hilar mass with a middle lobe collapse
  • CT scan of the chest/abdomen/pelvis revealed a 4.9 x 5.4 cm left upper lobe mass with bilateral hilar and mediastinal lymphadenopathy
  • CT abdomen/pelvis negative for metastatic disease
  • PET/CT confirmed activity in the lung and lymph nodes
  • MRI of the brain was negative for metastatic disease
• CT-guided biopsy of the left lung mass revealed a differentiated invasive squamous cell carcinoma
• Molecular testing: PD-L1 20%
• Staging: T2bN3M0—IIIB
• ECOG PS 1

Treatment

• Concurrent chemoradiation with weekly carboplatin-paclitaxel
• Imaging 6 weeks after completion showed response in the lung and lymph nodes
• Durvalumab consolidation: 4 cycles with continued tumor control on imaging
• Developed dyspnea and cough after 8 cycles