Local consolidative therapy shows benefit in oligometastatic NSCLC

Patients with oligometastatic non–small cell lung cancer (NSCLC) have better outcomes when treated with local consolidative therapy than with maintenance therapy or observation, based on updated results from a phase 2 trial.

The randomized study showed that both median progression-free and overall survival were better in patients who received radiotherapy or surgery instead of maintenance therapy or observation, reported lead author Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings build on earlier results that showed the positive impact of local consolidative therapy (LCT), the investigators noted.

“The trial was closed early after it demonstrated an observed 8-month benefit in [progression-free survival] for patients who received LCT relative to patients who received maintenance therapy or observation,” the investigators wrote in Journal of Clinical Oncology.

After early closure, 49 patients remained in the dataset. All had metastatic NSCLC with three or fewer metastases that did not progress for at least 3 months after first-line systemic therapy. Most patients had adenocarcinoma (80%). Patients were randomly divided in a 1:1 ratio between radiotherapy or surgery (LCT) for all active disease sites or maintenance therapy/observation (MT/O). Progression-free survival was the primary endpoint. Overall survival and several other secondary endpoints were also evaluated.

Data analysis showed a clear benefit of LCT. Continuing the previously reported trend, median progression-free survival was extended in the LCT group, compared with the MT/O group (14.2 vs. 4.4 months; P = .022). Similarly, median overall survival showed a significant improvement (41.2 vs. 17.0 months; P = .017). Median time to appearance of new lesions also supported the advantage of LCT over MT/O, albeit with less statistical significance (14.2 vs. 6.0 months; P = .11).

The investigators suggested several mechanisms behind the efficacy of LCT, including elimination of treatment-resistant cells, potentiation of systemic therapy, and elimination of the residual tumor as a driver of distant micrometastatic disease. “Notably,” the investigators wrote, “these mechanisms are not mutually exclusive, and more than one could contribute to the benefits of LCT.”

“[A]lthough these data are compelling ... we emphasize that future studies should be supported to definitively assess the role of LCT in larger populations (e.g., phase III trials such as NRG-LU002) and in the context of novel systemic therapies,” the investigators concluded.

The study was funded by MD Anderson Cancer Center, The Mohaymen Sahebzadah Family Philanthropic Grant, and the National Cancer Institute, National Institutes of Health. The authors disclosed relationships with Merck, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Gomez et al. J Clin Oncol. 8 May 2019. doi:10.1200/JCO.19.00201.

Patients with oligometastatic non–small cell lung cancer (NSCLC) have better outcomes when treated with local consolidative therapy than with maintenance therapy or observation, based on updated results from a phase 2 trial.

The randomized study showed that both median progression-free and overall survival were better in patients who received radiotherapy or surgery instead of maintenance therapy or observation, reported lead author Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings build on earlier results that showed the positive impact of local consolidative therapy (LCT), the investigators noted.

“The trial was closed early after it demonstrated an observed 8-month benefit in [progression-free survival] for patients who received LCT relative to patients who received maintenance therapy or observation,” the investigators wrote in Journal of Clinical Oncology.

After early closure, 49 patients remained in the dataset. All had metastatic NSCLC with three or fewer metastases that did not progress for at least 3 months after first-line systemic therapy. Most patients had adenocarcinoma (80%). Patients were randomly divided in a 1:1 ratio between radiotherapy or surgery (LCT) for all active disease sites or maintenance therapy/observation (MT/O). Progression-free survival was the primary endpoint. Overall survival and several other secondary endpoints were also evaluated.

Data analysis showed a clear benefit of LCT. Continuing the previously reported trend, median progression-free survival was extended in the LCT group, compared with the MT/O group (14.2 vs. 4.4 months; P = .022). Similarly, median overall survival showed a significant improvement (41.2 vs. 17.0 months; P = .017). Median time to appearance of new lesions also supported the advantage of LCT over MT/O, albeit with less statistical significance (14.2 vs. 6.0 months; P = .11).

The investigators suggested several mechanisms behind the efficacy of LCT, including elimination of treatment-resistant cells, potentiation of systemic therapy, and elimination of the residual tumor as a driver of distant micrometastatic disease. “Notably,” the investigators wrote, “these mechanisms are not mutually exclusive, and more than one could contribute to the benefits of LCT.”

“[A]lthough these data are compelling ... we emphasize that future studies should be supported to definitively assess the role of LCT in larger populations (e.g., phase III trials such as NRG-LU002) and in the context of novel systemic therapies,” the investigators concluded.

The study was funded by MD Anderson Cancer Center, The Mohaymen Sahebzadah Family Philanthropic Grant, and the National Cancer Institute, National Institutes of Health. The authors disclosed relationships with Merck, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Gomez et al. J Clin Oncol. 8 May 2019. doi:10.1200/JCO.19.00201.

Patients with oligometastatic non–small cell lung cancer (NSCLC) have better outcomes when treated with local consolidative therapy than with maintenance therapy or observation, based on updated results from a phase 2 trial.

The randomized study showed that both median progression-free and overall survival were better in patients who received radiotherapy or surgery instead of maintenance therapy or observation, reported lead author Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings build on earlier results that showed the positive impact of local consolidative therapy (LCT), the investigators noted.

“The trial was closed early after it demonstrated an observed 8-month benefit in [progression-free survival] for patients who received LCT relative to patients who received maintenance therapy or observation,” the investigators wrote in Journal of Clinical Oncology.

After early closure, 49 patients remained in the dataset. All had metastatic NSCLC with three or fewer metastases that did not progress for at least 3 months after first-line systemic therapy. Most patients had adenocarcinoma (80%). Patients were randomly divided in a 1:1 ratio between radiotherapy or surgery (LCT) for all active disease sites or maintenance therapy/observation (MT/O). Progression-free survival was the primary endpoint. Overall survival and several other secondary endpoints were also evaluated.

Data analysis showed a clear benefit of LCT. Continuing the previously reported trend, median progression-free survival was extended in the LCT group, compared with the MT/O group (14.2 vs. 4.4 months; P = .022). Similarly, median overall survival showed a significant improvement (41.2 vs. 17.0 months; P = .017). Median time to appearance of new lesions also supported the advantage of LCT over MT/O, albeit with less statistical significance (14.2 vs. 6.0 months; P = .11).

The investigators suggested several mechanisms behind the efficacy of LCT, including elimination of treatment-resistant cells, potentiation of systemic therapy, and elimination of the residual tumor as a driver of distant micrometastatic disease. “Notably,” the investigators wrote, “these mechanisms are not mutually exclusive, and more than one could contribute to the benefits of LCT.”

“[A]lthough these data are compelling ... we emphasize that future studies should be supported to definitively assess the role of LCT in larger populations (e.g., phase III trials such as NRG-LU002) and in the context of novel systemic therapies,” the investigators concluded.

The study was funded by MD Anderson Cancer Center, The Mohaymen Sahebzadah Family Philanthropic Grant, and the National Cancer Institute, National Institutes of Health. The authors disclosed relationships with Merck, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Gomez et al. J Clin Oncol. 8 May 2019. doi:10.1200/JCO.19.00201.