Erlotinib + BSC fares better than BSC alone for gall bladder cancer

The addition of erlotinib to best supportive care (BSC) provided better survival benefit than BSC only in individuals with unresectable/metastatic gall bladder cancer (GBC) with poor performance status (PS), according to a phase II/III open-label study.

GBC is the most aggressive biliary tract cancer, with the shortest median OS from time of diagnosis. [Clin Epidemiol 2014;6:99-109; Oncologist 2010;15:168-81] For those with unresectable disease, median survival is reportedly only up to 11 months. [J Clin Oncol 2010;28:4581-4586; N Engl J Med 2010;362:1273-1281] Outcomes could be bleaker for GBC patients with poor PS, as median survival can only be a month. [Cancer 1978;42:330-335]

“Currently, there is no standard of care for … patients with unresectable/metastatic GBC [with poor PS] … Being unfit for chemotherapy, these patients only receive BSC, [but this has] a very dismal outcome,” noted Dr Babita Kataria from the National Cancer Institute – All India Institute of Medical Sciences, Haryana, India, in the poster discussion at ESMO GI 2022.

Kataria and colleagues evaluated 105 participants from tertiary healthcare centres in India who had histologically confirmed unresectable/metastatic GBC with adequate organ function and ECOG* PS III. They were randomized 1:1:1 to receive BSC either alone or in combination with erlotinib 150 mg OD or capecitabine 625 mg/m² BD. [ESMO GI 2022, abstract PD-9]

In the comparison between erlotinib + BSC vs BSC alone, overall survival (OS) was better with the former than the latter after a median follow-up of 10 months (median, 3.84 vs 1.77 months; hazard ratio [HR], 0.50; p=0.02).

Twelve patients in the erlotinib arm reported grade 3/4 toxicities, the most common being diarrhoea and skin rash. There were no treatment-related deaths tied to erlotinib.

“Erlotinib + BSC has statistically significant and clinically meaningful absolute improvement of OS by 2.07 months compared with BSC alone in patients with unresectable/metastatic GBC with ECOG PS III who are unfit to receive chemotherapy, with an acceptable toxicity profile,” said the investigators.

Secondary outcomes

The erlotinib arm still trumped the BSC-only arm in terms of progression-free survival (2.13 vs 0.75 months; HR, 0.44; p=0.002), disease control rate** (58 percent vs 15 percent; p=0.004), and clinical benefit rate (72 percent vs 30 percent; odds ratio, 5.19; p=0.005) at 6–8 weeks.

In the quality-of-life (QoL) analysis using the EORTC QLQ-C30 BIL21*** questionnaire, erlotinib + BSC was generally better compared with BSC only at 6–8 weeks. From baseline eating scores of 75 in both arms, the score dropped to 46 in the erlotinib arm but rose to 92 in the BSC-only arm. For jaundice, the score in the erlotinib arm dropped from 11 to 0, whereas in the BSC-only arm, the score jumped from a baseline of zero to 33.

Although both arms saw reductions in pain and anxiety scores, the reductions were greater in the erlotinib (from 67 to 29 [pain] and from 67 to 33 [anxiety]) compared with the BSC-only arm (from 71 to 58 and from 67 to 58, respectively).

For tiredness, the score in the erlotinib arm dropped from 78 at baseline to 47 at 6–8 weeks. In the BSC-only arm, the score of 100 was sustained throughout the two timepoints.

Overall, increasing scores in the questionnaire parameters denote worse QoL, the investigators noted.