LUMINAL B PROSTATE CANCER RESPONSE BETTER TO CHEMOTHERAPY

Patients with luminal B prostate cancer have better overall survival (OS) when treated with upfront docetaxel, according to a new study examining basal-luminal subtypes and response to therapy from the E3805 CHAARTED trial (Abstract 162). Luminal B disease is associated with poorer OS in patients treated with androgen deprivation therapy (ADT) alone.

“There is a critical need to identify and better understand patients who do and do not benefit from upfront chemotherapy or hormonal therapy, in order to guide optimal therapy selection,” said Anis A. Hamid, MBBS, of the Dana-Farber Cancer Institute, who presented results of the new study during the Genitourinary Cancers Symposium on February 13. He said that previous research has indicated evidence for cells of both luminal and basal lineage giving rise to prostate cancer“Indeed, across cancers, there are commonalities between luminal and basal tumors that seem to transcend the organ of origin,” Dr. Hamid said.

The E3805 CHAARTED trial included 393 patients with metastatic hormone-sensitive prostate cancer treated with ADT alone, and 397 patients treated with ADT plus docetaxel. For the new analysis, the researchers included a total of 160 patients from the larger cohort: 76 from the ADT-alone group and 84 patients from the ADT plus docetaxel group. The groups were well balanced with regard to Eastern Cooperative Oncology Group performance status, prostate-specific antigen level at the start of ADT, prior local treatment, and tumor volume. None of the docetaxel group had received prior ADT, compared with 5.3% of the ADT-alone group (p = 0.049).

Basal subtype was most common in this cohort, accounting for 52.1% of the 160 patients. This was followed by luminal B subtype, at 46.1%, whereas only 1.8% of the patients had luminal A subtype. Dr. Hamid emphasized that this was substantially different from that seen in localized disease, where basal, luminal A, and luminal B subtypes are relatively evenly distributed.

In the ADT-alone group, OS was poorer in those with luminal B disease, at a median of 29.8 months versus 47.1 months in those with basal subtype; on a multivariate analysis, the hazard ratio (HR) was 1.79 (95% CI [0.99, 3.24]); p = 0.055). In the ADT plus docetaxel group, the OS was similar across the subtypes, at 52.1 months with luminal B and 49.2 months with basal subtype, for a multivariate HR of 0.88 (95% CI [0.47, 1.67]; p = 0.70).

There was a differential benefit from the addition of docetaxel based on disease subtype. In patients with basal-subtype disease, the median OS was 49.2 months with docetaxel and 47.1 months with ADT alone, for an HR of 0.85 (95% CI [0.47, 1.55]; p = 0.60). In patients with luminal B disease, the median OS was 52.1 months with docetaxel and only 29.8 months without it, for an HR of 0.45 (95% CI [0.25, 0.81]; p = 0.007). This result was confirmed in a subset of patients with high tumor volume.

There was no difference with regard to the time to castration-resistant prostate cancer (CRPC) based on luminal-basal subtype. The addition of docetaxel extended the time to CRPC in both luminal B and basal subtypes.

“Collectively, these data support our hypothesis stemming from preclinical modeling of taxane response by luminal-basal subtype,” Dr. Hamid concluded. “These data also emphasize the critical need for further biologic correlation.”

Dana E. Rathkopf, MD, of Memorial Sloan Kettering Cancer Center, was the discussant for the abstract. “It’s very important to state [that] this is not a one-size-fits-all situation with basal and luminal subtypes,” she said. “The subtypes across carcinomas may respond differently to treatment.”

“I think we would all agree that further validation is needed before we move this into clinical practice.” – Dr. Dana E. Rathkopf

Dr. Rathkopf cautioned that because luminal B subtype fares worse with ADT alone, it is possible that this makes the benefit of docetaxel in these patients appear inflated. “I think we would all agree that further validation is needed before we move this into clinical practice,” she said. “There are probably additional clinical and molecular factors that we need to incorporate into these types of models.”

— Dave Levitan