Counseling Patients on Next Steps After Chemoradiation for Stage III NSCLC

Garrett B. Sherwood, MD (Moderator)

Medical Oncologist

Novant Health Cancer Institute - Forsyth

Winston-Salem, NC

CASE SUMMARY

A 63-year-old man presented to his physician with intermittent cough and difficulty breathing on exertion. He had a history of hypothyroidism, which was managed on levothyroxine; and chronic obstructive pulmonary disease (COPD), which was managed on inhalers. He recently quit smoking and has a 40-pack-year history. His ECOG performance status was 1. Complete blood count, chemistries, and creatinine were within normal limits.

A chest CT scan showed a 3.1-cm spiculated left upper lobe (LUL) mass and 2 enlarged left mediastinal lymph nodes (stations 4L and 7), measuring 2.5 cm and 1.7 cm, as well as moderate emphysema. A PET scan confirmed lung lesion and mediastinal lymphadenopathy without evidence of distant metastases. His brain MRI was negative. Pulmonary function tests showed a forced expiratory volume of 1.2 and a diffusing capacity of the lungs for carbon monoxide of 35%.

Bronchoscopy with transbronchial lung biopsy of LUL mass and lymph node sampling via endobronchial ultrasound revealed adenocarcinoma at primary site, with positive nodes in stations 4L and 7. His cancer staging was T2aN2M0, stage IIIA.

In this patient, the results of molecular testing show negative results for driver oncogenes in EGFR, ROS1, BRAF, ALK, RET, MET, ERBB2, NTRK, and KRAS. His PD-L1 expression level is 1%.

Based on patient preference and extent of mediastinal disease plus symptomatic COPD, the patient’s cancer was deemed unresectable, and he was referred for consideration of concurrent chemotherapy and radiation. He underwent therapy with cisplatin/pemetrexed and concurrent thoracic radiotherapy to 66 Gy. He tolerated therapy relatively well, excepting grade 2 esophagitis, which was treated medically. A restaging CT scan showed a partial response with shrinkage of the primary and nodal lesions. No evidence of distant spread was observed.

GARRETT B. SHERWOOD, MD: In terms of timing of the restaging CT scan, for those of us who are working closely with the radiation oncologist, who owns that? Are they ordering it? Are you ordering it as the medical oncologist? Are you getting a CT chest, abdomen, or pelvis scan with contrast, or are you getting a CT chest scan without contrast?

SANDEEP PANDIT, MD: Our interventional radiologist, medical oncologist, and I usually wait for [approximately] 4 to 6 weeks after the radiation is done. We do a CT scan with contrast.

SUKHMANI GILL, MD: I wait 4 weeks after and typically do a CT scan with contrast. If the radiation oncologist sees the patient, sometimes they’ll order the scan as well.

RUILING YUAN, MD: In my practice, the medical oncologist orders CT chest with contrast. I [often] try to follow the protocol ordering within 3 to 4 weeks, but our radiation oncologist always say it’s too soon.

DISCUSSION QUESTION

• In general, what is your next step after the last dose of radiation for patients receiving chemoradiation, assuming restaging CT scan shows no evidence of progressive disease?

SHERWOOD: I talk to patients about durvalumab [Imfinzi] as they’re finishing concurrent chemoradiation. If I’m seeing them weekly, by their fifth or sixth week of treatment, they’re dealing with adverse events [AEs], but I prepare them for the next step. I’ve always found it hard to know how to talk to a patient about the total duration of therapy. If you meet someone like this patient at the very beginning, do you tell them right up front that after their 8 weeks of concurrent chemoradiation, you’re going to recommend up to 1 year of adjuvant therapy or consolidation therapy? I tend to not focus on that initially and focus more on getting the patient to understand the stage, the diagnosis, and the rationale behind concurrent chemoradiotherapy. Then I focus more on the data for consolidation durvalumab, how immunotherapy is different, and why we think that it works well after concurrent chemoradiotherapy.

When are you mentioning durvalumab to your patients? Is it only after their scan is done and you see that they’re a candidate, or are you mentioning it before? Is that something you want the radiation oncologist to talk to them about, or is that something you feel is best handled by a medical oncologist?

MAURIZIO BENDANDI, MD: I mention it while they are receiving chemotherapy. Then a patient like this will ask me [whether] they have PD-L1 [expression greater than 1%], after they understand what PD-L1 is.

KWABENA OSEI-BOATENG, MD: While I do the discussion about concurrent chemoradiation, I always also mention that we’re going to do a restaging scan [after]. If they have a good response, then we will do the maintenance phase with durvalumab. Like you, I don’t go into a lot of detail about it. I just mention it so it’s on their radar. After they come back with the scan, we go into a more detailed discussion about it.

PANDIT: I do the same thing. I mention the whole treatment package but go into detail at each step when the treatment is about to start or just before.

GILL: I’m doing something very similar. Like you said, I also try to focus on how this is very different from what they’re getting now, so that they know immunotherapy works in a different way. I focus on that more and tell them they have done the hardest part, so they don’t need to worry.

DISCUSSION QUESTION

• How long do you typically continue durvalumab?

SHERWOOD: Do you get patients through 12 whole months? I do try to push patients. There’s treatment fatigue. [Patients] get tired of coming to see me…. We have patients who say, “I want to be done. I’ve done 9 months; do I have to keep going?” Is that something you deal with? Patients who are a year into treatment and they have a few months left, but they don’t want to keep going.

BENDANDI: In my experience, the opposite happens. If I tell them that after 12 months…they don’t want to stop.

SHERWOOD: It does feel arbitrary to stop at 1 year, so you’re right.

BENDANDI: Also, what happens if the CT scan shows progression 3 or 6 months later? Would that happen if they stayed on medication? We don’t know, but you don’t feel good if [that happens when] they weren’t on medication.

SHERWOOD: You’re right.

OSEI-BOATENG: Most of the time—maybe because we had discussed that it’s going to be a year—I haven’t had as many patients on maintenance durvalumab wanting to continue like in other diseases [such as] melanoma, or where they want to continue after they’ve been on it for a longer period of time. When I’ve had to stop it, it hasn’t typically been because they didn’t want to continue. It’s been because there’s been some AEs that have made us discontinue treatment. It doesn’t happen often, but I’ve stopped it on a couple occasions because of AEs.

PANDIT: I’ve had a couple of patients with grade 3 or higher musculoskeletal AEs. They got tired after 9 to 10 months and said they couldn’t do it anymore and wanted to come off therapy. Otherwise, patients typically complete therapy.

SHERWOOD: For the subgroup analysis, durvalumab is favored in almost every single subgroup, apart from in patients with PD-L1 of less than 1%.¹ The total number of patients in that group is small. I believe the European Union, at least for a time, did not approve durvalumab in that patient population, based on the unplanned subgroup analysis, which I think is interesting.² My practice for the driver mutant–negative patients is generally to offer durvalumab. Is anyone not offering durvalumab based on PD-L1?

CHARLES KUZMA, MD: No, but I’d like to see a study that gets at that question.

_REFERENCES

_{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}

_{European Commission approves Imfinzi for locally-advanced, unresectable NSCLC. News release. AstraZeneca. September 24, 2018. Accessed June 26, 2023. https://tinyurl.com/y56j5eby}