Maria Werner-Wasik, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, discusses the rapidly changing standards of care for patients with stage III non-small cell lung cancer with the advent of preoperative combination chemotherapy and immunotherapy.

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Transcript:

Hello, my name is Maria Werner-Wasik. I'm a thoracic radiation oncologist at Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania. The topic of my brief presentation at 2023 ACRO Summit is preoperative treatment for stage III non-small cell lung cancer. As many of you know, currently most patients with stage III non-small cell lung cancer, particularly unresectable patients, are being treated with definitive intention with concurrent chemoradiotherapy, which means that they will receive daily thoracic radiation, 60 to 70 Gray total dose, in daily 2 Gray fractions directed to their tumor and the involved lymph nodes, if any. And that is usually given with chemotherapy concurrently, which means that most likely patients will be receiving weekly dose of some type of standard chemotherapy, frequently being carboplatin and paclitaxel in once weekly doses. For those patients who have no progressive disease after chemoradiotherapy, which will be a vast majority of them, they would receive then consolidation immunotherapy based on the PACIFIC trial, most likely being durvalumab for several months as intravenous infusions.

Median survival time for patients treated that way is quite remarkable compared to prior historic benchmarks and currently is being quoted at about 47 months. In addition, a subgroup of patients with stage IIIa non-small cell lung cancer, is being offered surgery in addition to either pre-operative chemoradiotherapy again for 5 to 6 weeks or chemotherapy alone, followed then by surgery 3 to 8 weeks after completion of this induction or neoadjuvant treatment. In general, in most institutions, such trimodality or bimodality therapy including surgery, is reserved for patients who are younger, who have a single nodal level in mediastinum or N2 involvement, do not have N3or contralateral mediastinal or hilar, or supraclavicular disease, who had good performance status and whose lymph nodes are non-bulky. While the definition of bulky lymph nodes in the mediastinum is not well established, frequently is being quoted as less than 3cm being non-bulky or less bulky.

However, this standard of care, which I described here, has been rapidly changing over the last several months really or less than a year, and that's based on the new and very exciting data coming out of several phase 2 and recently phase 3 trials where preoperative therapy prior to surgery consisting of combination of chemotherapy with immunotherapy has been demonstrated to be remarkably efficient in prolonging event-free survival, progression-free survival for patients, and increasing the pathologic response rate based on the evaluation of the tumor resected during surgery following this pre-operative therapy. The studies which created a lot of excitement are the CheckMate study 816 and the NADIM II trial. CheckMate 816 took patients with stage III non-small cell lung cancer starting from stage Ib to stage III, and the second NADIM II trial was a randomized study in which patients who were included were only those with stage IIIa lung cancer and some with stage IIIb also.

Randomization included chemoimmunotherapy compared to chemotherapy alone in both of those trials I'm quoting. And what was observed was that in the CheckMate study, the major pathologic response rates were actually 12 times higher in the combined modality or experimental arm of chemoimmunotherapy. Then in the chemotherapy alone arm, the survival data are not fully mature for either study, but the survival median survival time has not been reached. For example, in the NADIM II trial at 2 years was quoted as 85% for combined modality arm versus 65% or so for the chemotherapy alone arm. So those are major, major differences and major improvement.

Source:

Werner-Wasik M. “Preoperative Therapy for Stage III Non-Small Cell Lung Cancer: The Big Revival.” Presented at: Radiation Oncology Summit: ACRO 2023; March 15-18, 2023; Lake Buena Vista, FL.