How I will treat my next patient

PROs in lung cancer and how to administer trastuzumab


 

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

Dr. Alan P. Lyss, an oncologist who practices in St. Louis

Dr. Alan P. Lyss

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.

These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

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